Beta Fulltext view is in preview — article structure may vary. Browse all articles
Contents
Virology & Immunology Journal Research Article 36 min read

Cultural Properties of Viruses and Design of Safe Recombinant Vaccines and Virus Gene Constructs on their Basis

Iskra V Sainova*
* Corresponding author
ISSN: 2577-4379  10.23880/vij-16000226  Received: November 07, 2019  Published: December 03, 2019
 — views
 112 references
PDF
Keywords
Cell Cultures Cell Lines Stem/Progenitor Cells Avian Pox Viruses Recombinant Avian Pox Viruses Vaccines Virus Gene Constructs
Abstract

The results from various studies have shown a lot of particular differences in the mean length of telomere regions of chromosomes from stem cells at different stages of development and ifferentiation. The differences between stem/progenitor cell types in DNA-repair and telomere maintenance pathways have been found as co-evolved with the cell proliferation, differentiation, transformation, aging and life span. Studies on these cells are often focused on their ability for self-renewal. On the other hand, however, like damages in these processes have been characterized cancer and leukemia. Hence, the detailed study of these processes is necessary for understanding of the mechanisms, leading to repair and regeneration of mutated, damaged and/or destroyed cells, tissues and organs. As a new perspective in this aspect has been established the use of cell vectors, obtained by transduction of genes in stem/progenitor cells, by virus gene constructs. Avian pox viruses (APVs) can replicate in different cell-culture systems: primary embryo cells, diploid cell clones and permanent cell lines. The needs for production of more safety vaccines have challenged the research to find suitable cell-culture systems for their cultivation. In the last years abilities for replication of these viruses in nonavian cells and their possible application for vaccination of non-avian species were revealed. Because that, different cell culture systems have been used for production of recombinant APVs (rAPVs) as a base for construction of recombinant vaccines against different diseases in birds and mammals, including people. In such way, the avian cell-culture systems could be used for production of rAPV vaccines against diseases in birds, and the mammalian cell-culture systems – for production of such vaccines against diseases in mammals. In addition, the permanent cell lines possess a lot of advantages in comparison with the primary embrional cells and could be also used for isolation and detection of APVs, as well as for diagnostic aims. Techniques, developed for construction of recombinants of vaccinia virus, could be adapted in the construction of recombinant avian pox viruses (rAPVs), especially of recombinant fowlpox viruses rFWPVs) andrecombinant canarypox viruses (rCNPVs). These abilities make possible event the possibility of treatment of some types of tumors in people.

Introduction

Studies on the biology of the stem/progenitor cells are often focused on their self-renewal and differentiation [1]. It is important to note that the efficiency of DNA-repair varies greatly among different stem cell types [2]. Stem cells in young and middle-aged mice have been found to be rarely in the S/G2/M phases of the cell cycle, but in old mice - frequently in the cycle [2, 3]. One of the possible hypotheses has been that the unexpected proliferation in old mice might be related to the increased incidence of leukemia in old mice. Hence, these cells change with age. The high self-renewal potential of the stem/progenitor cells in in vitro-conditions makes them strong candidates for delivering of genes, as well as for restoring organ systems function have been found to be included in these processes. This understanding could be applied toward the ultimate goal of using stem/progenitor cells not just for various forms of therapy, but rather as a tool to discover the mechanisms and means to bring, reconstituting them from old and young individuals has exhibited indistinguishable progenitor activities in vivo and in vitro [4, 5]. In using of experimental mice, it has been determined that, after mobilization with receptor antagonist, exited from bone marrow stem/progenitor cells, have transited blood and engraft in open niches in partner marrow. The niche has been proposed as an environment that insulates stem cells from various stimuli and maintains them in a quiescent state [6]. The properties of “malignant stem cells”, have outlined initial therapeutic strategies against them.

The differences between stem/progenitor cell types in DNA-repair and telomere maintenance pathways have been found as co-evolved with cell proliferation, transformation, aging and life span [3, 4]. This idea has given rise to the notion that many aspects of normal aging could primarily reflect limitations in DNA-repair and telomere-maintenance pathways in the stem/progenitor cells [7]. In humans, the levels of enzyme telomerase in the stem cells have been established under extremely tight control, as it has been illustrated by the bone marrow failure in patients with telomerase deficiencies. In the biology of human stem/progenitor cells, telomerase has been proposed to play an important role in the repair of guanine-rich DNA-regions [4]. These cells have been defined as pluripotent, with self-renewal capacity [3, 4, 7]. Recent studies have shown striking differences in the mean length of the telomere repeat sequences at the chromosomes’ ends from human stem/progenitor cells at different stages of development [3, 4, 7, 8]. The most likely expansion for these observations has been that stem/progenitor cells, which, like all other somatic cells, lose telomere DNA upon each cell division. Clinical use of cultured human mesenchimal stem cells has begun for cancer patients and the recipients have received autologous or allogeneic stem cells [9, 10, 11].

The necessity of production of more secure and safer vaccines against the poxvirus diseases imposed studies for searching of suitable cell-culture systems for replication of these viruses. For the first time such virological method has been suggested in 1949. A process of propagation of fowl pox virus (FWPV) in cell cultures (CCs) with epithelial origin, seeded as roller cultures has been established, and the authors have observed osmiophilic cytoplasmic inclusions [12, 13, 14]. This process has been confirmed by the death of the cells for some days and also by the high virus titer in the supernatant. The same authors have done a message about the propagation of FWPV in chicken embryonic fibroblasts (CEFs), seeded as roller cultures [15]. The roller cultures are suitable for cultivation and propagation of avian pox viruses (APVs), because the constantly change of the liquid and the air phase ensures more favorable conditions for virus replication. The changes, which have been observed in the roller cultures, have been the same, which were characteristic for CCs, infected in monolayer (specific cytoplasmic inclusions, vacuolization of the cytoplasm, rounding of the cells and their detachment from the substrate). One of the most important factors is the rolling speed. For example, the amount of produced by vaccinia virus pathological changes in cultures, rolled at 96 rpm, has been significantly enhanced in comparison with cultures, rolled at 2 rpm or held stationary [12, 13, 14, 15].

Vaccines, based on virus genome constructs, have been found to suggest new possibilities for effective control of different diseases in birds and mammals, including humans [16, 17, 18, 19, 20, 21, 22, 23]. Both RNA- and DNA-viruses could be used as virus vectors. Virus vector vaccines, received by insertion of genes, which code define sequences of different viruses and epitopes, have possessed a lot of advantages in comparison with the attenuated, died and subunit vaccines. The fact that the recipients could be immunized against specific antigens has been characterized as one of the most important features of the live virus vectors. Possible modifications have been proven to be an increasing of the expression level of the foreign antigen by a change in the promoter or in the insertion site, in the target repeats of the virus vector, in the expressing antigen and/or in the co- expressing immunomodulator proteins [19, 20, 21, 22]. Because of the large size of the genome, the pox viruses have been found to be able to express more than one foreign gene for creation of polyvalent vaccines, as well as some non- essential genes and some regulating sequences in the genome of the fowl pox virus (FWPV) [20]. As a necessary has been established the insertion of foreign genes to be done on such way that the replication of the parent virus not be concerned, but on the other hand, the last has been characterized as necessary for an optimal expression of the inserted genes [24, 25, 26, 27, 28].

Cultivation of Avian Pox Viruses in Cell Cultures

A successful cultivation of FWPV, pigeon pox virus (PGPV) and canarypox virus (CNPV) has been done in mammalian CCs was done after consistent adaptation passages in chicken and duck embryo cells [16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54]. CCs have also been used for differentiation of APVs (in antigenic composition, as well as in genetic respect), for diagnostic purposes and for production of recombinant APVs (rAPVs) [18, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 44, 46, 47, 48, 49, 50, 51, 52, 53, 54]. An antigenic differentiation by production of monoclonal antibodies after concentrating of the supernatants of CCs, infected with PGPV and CNPV has been done. For this aims, homologous recombination by using of plasmid vectors, containing suitable promoter, and a segment from the FWPV DNA, coding non-essential region of the virus genome has been used [43]. It has been inserted the gene, coding the enzyme β-galactosidase from E. coli in the produced recombinant APV (rAPV) [44]. rFWPVs, expressing genes for the haemagglutinin (HA) of the avian influenza virus have been constructed [20, 21, 22]. Later rFWPVs have been used for first time for in ovo- inoculation [23]. In these cases, the expression of haemagglutinin-neuraminidase (HA-NA) and of the fusion glycoprotein (F) in CEFs has been proved by immunohistochemical assay [23, 24].

In 2001, a stable rFWPV, expressing the C-terminal region (consisting of 119 aminoacid remainders) of the nucleocapside protein (N) of the IBV, strain Ch3, has been constructed by insertion of a coding sequence on tk gene region of the FWPV by homologue recombination [25]. The inserted nucleocapside protein has been expressed in CEFs under the control of the vaccinia virus promoter P7.5. For genetic differentiation of APVs polymerase chain reaction (PCR) has been added. In this way, a gene, coding protein with molecular weight 39 kDa from adapted on CCs TKPV, has been identified. Before that the propagation of FWPV and the provoked pathological changes in CEFs has been observed. These changes have been observed at the third day after the inoculation of the cultures, and they have been expressed mainly in vacuolization of the cytoplasm, rounding of the cells and necrosis. Besides that, a presence of cytoplasmic eosinophilic inclusions has been demonstrated [25– 50,53-55]. On the fourth day post inoculation (p. i.) yellow and greenish fluorescence in staining with acridine orange has been observed, and on the sixth day p. i. – only green fluorescence of the cytoplasmic inclusions. These results have proved the presence of virus DNA in the cytoplasm of the infected cells. Besides that, on the sixth day p. i. the authors established that the nuclei and the cytoplasmic inclusions in the cells stained in pink (a positive reaction by the Fewlgen test), which was also an indication that these inclusions were composed by virus DNA. The cultivation of APVs in CCs could be also used for another diagnostic methods: immunodiffusion in agarose gel, immunofluorescence, virus neutralisation, passive haemagglutination, enzyme-linked immunosorbent assay (ELISA), immunoperoxidase reaction.

In the last years if the 20th century have been made experiments for adaptation and propagation of APVs in mammalian CCs [56, 57, 58]. The experiments for propagation of FWPVs in monkey (Vero and CV-1) and human (HeLa and MRC-5) permanent cell lines (CLs) after their previous cultivation on CEFs, have shown that a probability for production of mature virions exists [56]. Later similar experiments were done with the CLs MDBK and EBTr, derived from embrional bovine kidney and trachea, respectively [57, 58]. The authors have observed a slow CPE, which was also an indication that the APVs replicate productively in a reduced number of infected mammalian cells. Results, which demonstrated the activity of expression of the inserted from Esherichia coli gene for the enzyme β-galactosidase in CEFs, as well as in the Vero CL, infected with such rAPVs, have been received. Besides that, it has been shown that rFWPVs and recombinant canarypox viruses (rCNPVs), which contained genes, coding some glycoproteins of the rabies virus and the measles virus, respectively, under the control of vaccinia virus H6-promoter, could express these genes in mammalian cells [55]. Similar results have been received about the activity of expression of the same enzyme gene in CCs of the Vero CL and in CEFs for studying of the expression of the late genes of the FWPV in the used CLs [56]. rFWPVs, expressing genes of some herpes viruses in mammals in CCs of the monkey CL Vero and of the human MRC-5 CL, have been produced. Although in inoculation of mammals and mammalian CLs with production of APVs of mature virus particles is not established or the level of the expression of late genes has been very low, the expression of early genes has been proven. In this way, a safety, which has been proven as an advantage in comparison with the using of virus recombinants, based on viruses, which has provoked productive infections, has been ensured. In contrast to vaccinia virus, CNPV, as well as all other APVs, have replicated productively in mammalian cells, without production of infectious virus particles. Because of these reasons, CCs of mammalian CLs have been used for replication of rFWPV, expressing the gene for HA of the human influenza virus. At the same time the authors have studied the effect of the co-expressed cytokines IL-2 and γ-IFN. Later, permanent mammalian CLs were applied for production of rFWPVs, expressing genes for the carcinoembrional antigen (CEA) and for the prostate-specific antigen (PSA), respectively [59]. Parallel with these genes, such for co-stimulating molecules have also been expressed.

Recombinant Vaccines, Based on Avian Pox Viruses

Vaccines, based on poxvirus vectors, have been found to leave a possibility for studying of the induction of the immune response [16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79]. Their applications have also been examined in tumor immunotherapy and gene therapy. By deletions of specific virus genes there have been received vaccines NYVAC, derived from attenuated vaccinia virus, Copenhagen strain, TROVAC, received from attenuated FWPV, and ALVAC, derived from a vaccine strain of CNPV. According to much literature data the recombinants, based on the CNPV genome are more effective in comparison with these, based on the FWPV. It has been considered that the creating of one of these recombinants is the first phase of the developing of such vaccine in humans [37]. In this case, in CNPV genome a gene, coding glycoprotein of the rabies virus has been inserted. The ability of recombinants, based on the CNPV genome, by induction of specific immunity against rabies in cats and dogs, fever in dogs, leucosis in cats and against the equine influenza virus, has been studied [32, 33, 34, 35, 36].

In humans, recombinant vaccines, based on the CNPV genome, which have expressed antigens of rabies, measles, Japanese encephalitis virus, as well as of some strains of the human influenza virus, have turned out harmless and high immunogenic. Besides that, recombinant canarypoxviruses (rCNPVs), containing sequences from HIV-1-genome, have been proven as promising vaccine “candidates”. rAPVs have also been applied for treating of some types of solid tumors in humans. Hence, infection with rAPVs could stimulates the cell and the humoral immune response against HIV, as well as against some tumor-associated antigens.

One of the most widely used expression systems in the molecular biology has been characterized vaccinia virus [17, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74]. However, in vaccination with vaccinia-virus- based recombinant vaccines – for example a danger for risk hosts, some problems have arised. The possible solution to this might be the use of APV vectors, for example, FWPV and CNPV for such aims in view of the next causes: abortive replication in mammalian cells; undergoing of the abortive replication in a small number of mammalian cells; high level of expression of foreign proteins; no danger of pathogenesis, as well as no natural immunity in humans [18, 21, 26, 27, 28, 30, 31, 32, 33, 34, 35, 36, 37, 38].

For expression of foreign genes, an integration of the foreign DNA in the poxvirus genome by homologous recombination or by a direct molecular cloning has been found to be necessary [39]. In both cases, plasmid vector constructions, containing the desired genes and at least one marker gene, have been used [40]. The necessity both types of genes to be controlled by suitable promoters has also been proven. For facilitation of this technique, a modified vaccinia virus genome, which has been proven as able to admit an direct insertion of DNA-fragments in the region of the vaccinia virus promoter without no forward steps of cloning, has been constructed [41]. The inserted gene has been amplified by polymerase chain reaction (PCR). Oligonucleotide primers, ensuring Sfi-site on the 5/-end, and Rsf-site on the 3/-end of the derived PCR- product have also been used [39, 40, 41]. In the digesting with the respective restrictases, the obtained PCR-product has been found to be connected with a synthetic promoter sequences in virus DNA-genome. However, intermediate plasmid constructions in this method haven’t been necessary. Techniques, used for construction of recombinants, based on vaccinia virus, might be easy applied for construction of recombinant vaccines, based on APVs [39, 40, 41, 42, 43, 44, 45, 46]. The possibility for insertion of some genes in the viral genome of the FWPV could allow the construction of polyvalent vaccines, as well as of vaccines, containing modificators of the immune response, as, for example, genes for lymphokines. For insertion of foreign genes in FWPV genome, tk, terminal repeats, as well as a site, homologous of this of the vaccinia virus, have been used. The homology between vaccinia virus and FWPV tk has been confirmed both at level nucleotides and aminoacides [40, 41].

Identification, cloning and mapping of main gene, expressed in the early and late stages of infection with FWPV, has also been realized. The necessity of the early function of this gene for construction of recombinant fowlpox viruses (rFWPVs) has been established. A poxvirus promoter for ensuring the expression of the inserted vaccine antigen, has also been proven to be necessary. It has been suggested that the strength of the used promoter could be an important condition in respect to the quality of the expressed vaccine antigen(s) and the inserted fragments could cause attenuation in some regions of the derived rFWPV. As one of the methods for refining of the recombinant vaccines, has been proven the using of natural or synthetic immunomodulating agents, some of which have been found to enhance the protection of the host, but other could repress the natural and the acquired immunity [30, 31, 32, 33, 34, 35, 36, 37, 38, 39]. As potential immunomodulating agents have been used cytokines (interferons and interleukines), because they are natural proteins, which have been found to be included in regulation of the immune response, as well as in the excitement of the live organisms. It has also been shown that the co-expression of the gene for IL-6 with gene for HA of the influenza virus in FWPV-vector stimulates the humoral immune response in mice. In this way, rFWPVs, expressing HA of the avian and human influenza virus, respectively, have been constructed. An additional possibility of vaccines, based on the FWPV and/or other APV vectors, has been the suggestion that these viruses could be suitable for vaccination of non-avian species. It has been established that the inoculation of mammalian cells with recombinants, based on APVs, results in expression of the foreign gene, and the inoculation of mammals with such recombinants – in induction of protective immunity.

Later, a strategy, based on immunization with DNA- plasmids and rFWPV, both coding common vaccine antigen has been developed [52, 53, 54, 55]. This method has been characterized as one of the most reliable vaccinations against HIV-1, and increased levels of T- cytotoxic lymphocytes (T-CTL) and anti-HIV-antibodies have been established. In this way, plasmid DNA and rFWPV have been between the most promising and most sure vaccine “candidates” against this virus strain, but the immunity, induced only by one of the vaccine components, might not be enough for ensuring of permanent protection against the infection with HIV-1.

Therapeutic Potential of Gene-Engineered Stem and Progenitor Cells

The evidences purporting the differentiation of the stem/progenitor cells into different cell lineages and evaluate the utility of these cells as cellular vectors for treating diseases, have been reviewed [80, 81, 82, 83]. Because these gene constructs haven’t shown cytotoxicity in normal human cells, their therapeutic efficacy has been suggested by the results obtained. For example, in testing of the role in survival by intratumoral treatment of tumor-bearing experimental animals with HSV, expression of IL-4 has been found to prolong their survival, whereas expression of IL-10 – to its reduction. To assess the strategy of combining oncolytic herpes simplex virus (HSV) therapy with immunomodulatory therapy as treatment for experimental colon cancer, the oncolytic HSV recombinant NV1023 and the IL-12- secreting oncolytic NV1042 virus have been evaluated in vivo and in vitro with respect to antitumor efficacy, and both NV1023 and NV1042 have had the potential to kill colon cancer cells at higher doses [79, 84]. Optimal survival of isolated plasma cells has been found to require stimulation by a combination of factors acting synergistically.

These results have strongly supported the concept that plasma cell survival depends on niches in which a combination of specific signals, including IL-5, IL-6, stromal cell-derived factor-1α, TNF-α, as well as ligands for CD44, provides an environment required to mediate plasma cell longevity. These findings could have implications in the development of specific second- generation cancer immunotherapy protocols. Immunization with several canarypox virus recombinants has protected BALB/c mice from a challenge with an isogenic and highly tumorigenic mouse fibroblast tumor cell line, expressing high levels of mutant p53 [35, 36, 37, 38]. On the other hand, in these experiments has been demonstrated that normal human mammary epithelial cells can be immortalized by transfection with virus DNA from human papilloma viruse strains 16 and 18 (HPV-16 and HPV-18), although these viruses have not been associated with breast cancer [69, 70]. The effective immortalization, as well as other pre-malignant changes, induced by transfection with HPV, have been found to be accompanied by chromosome changes, that may contribute to the partially transformed phenotypes. However, none of the cloned or pooled transfectants have been tumorigenic in the nude mouse assay. Immortalization has been experimentally separable from tumor-forming ability.

Lentiviruses have also been characterized as potentially advantageous compared to oncoretroviruses as gene transfer agents, as well as efficient tools for gene transfer stem cells, mainly because of their ability to infect non-dividing cells [85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100]. These of them, which contain transgene LacZ, have been found to achieve detectable β-galactosidase activity in rat arteries, albeit at a lower level compared with adenovirus vectors, mainly due to the lower concentration of lentivirus vector preparations [52, 53, 54, 55, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100].

It has also been suggested that by lentivirus vectors can be obtained using robust and tightly regulated knockdown of gene expression. In allogeneic stem cell transplantation, MSCs may be used for hematopoiesis enhancement [101]. It has also been proposed that resting HSCs may be transduced by lentivirus-based, but not MuLV-vectors, and these results have maintained their primitive phenotype, pluripotentiality, as well as, transgene expression in vitro [99, 100]. These findings have indicated a predictive value of gene transfer measurements to such LTC-IC for the design of clinical gene therapy protocols. Besides that, retrovirus-mediated transduction of human telomerase reverse transcriptase (hTERT) in human dermal microvascular embryonic cells (HDMECs) in vitro has resulted in cell lines that form microvascular structures after subcutaneous implantation in severe combined immunodeficiency (SCID) mice [102]. In addition, human bronchial, corneal and skin cells, expressing hTERT, have been found to be used to form organotypic cultures (bioengineered tissues) that express differentiation-specific proteins, demonstrating that hTERT by itself does not alter normal physiology. The production of hTERT-engineered tissues has offered the possibility of producing tissues to treat a variety of chronic diseases and age-related medical conditions that are due to telomere-based replicative senescence [2, 3, 4, 5, 6, 7, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100].

Telomere shortening has been found to inhibit mobilization of stem cells out of their niche, impaired hair growth and resulted in suppression of stem cell proliferative capacity in vitro. In contrast, overexpression of gene TERT in the absence of changes in telomere length has promoted stem cell mobilization, hair growth and stem cell proliferation in vitro. The effects of telomeres and telomerase on stem cell biology has been found to anticipate their role in cancer and aging [2, 3, 4, 5, 6, 7, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100]. Restoring of the telomerase activity as a putative therapeutic strategy has necessitated further study to elucidate the intricacies linking genetic and epigenetic modulations of gene hTERT. It has been shown that, when lesion repair is imperfect, immortal strand co-segregation leads to better preservation of the stem cell lineage than random chromosomal segregation. On the other hand, HIV-based vectors have been shown as promising tools for studies on gene functions in primary human B- lymphocytes and myeloma cells for the purposes of research, as well as the development of gene therapies [103, 104]. Successful use of this virus strain in treatment of tumors both directly and by tumor-targeted gene therapy vector has been obtained in transduction of human gene IFN-con1. Differentiation of engrafting HSCs to peripheral blood cells has been established to not be necessarily associated with a significant suppression of retroviral gene expression, which has accentuated the importance of empirically testing retrovirus vectors to determine lasting in vivo-expression [105, 106, 107, 108, 109]. As a useful tool for in vitro-tumor cell modeling and anticancer drug screening, as well as for cancer gene therapy, has been found alginate-poly-L-lysine-alginate microcapsule because of its influence on the proliferation, viability and metabolism of human cells, including anchorage-dependent MCF-7 breast cancer cells and primary fibroblasts, anchorage- independent leukemia cells K562, as well as cells in conventional culture have been used as a control [109]. Cells that have undergone immortalization via a crisis period of transformation by chemicals or viruses, as well as malignant cell lines in general, have had an ability to divide indefinitely. Mice, immunized with extracellular domain of oncogen Neu have been protected against a subsequent inoculation of MCNeuA cells, indicating that this cell line will be useful for evaluating cancer vaccine strategies. It has been demonstrated that primary myoepithelial cells from normal breast reduce breast cancer cell invasion and that this is mediated via modulation of both tumor cell and fibroblast function [109]. These results have emphasized the importance of the myoepithelial cell in controlling the breast microenvironment and focuses on the potential significance of the loss of this population with disease progression. According to other results, HIV-1-based vectors have appeared to be very efficient for delivering and expressing transgenes in MSCs [110, 111, 112]. HIV-1- based vectors in the context of MSCs may have clinical applications once the safety issues that are inherent to this vector system have been resolved.

Specific anti-gp100 T-cells, induced by in vivo- vaccination of experimental mice with recombinant Ad2CMV-gp100, have been found to be responsible for their protection. For example, in infection of malignant cells A549 with gene construct Ad-hEndo, in the infected tumor cells has been detected recombinant endostatin protein, and its inhibitory effect on endothelial cells growth has been shown.

Conclusion

It has been indicated that CCs from primary embryo cells, cell clones and CLs are convenient systems, which could be used for cultivation of viruses and for diagnostic aims, as well as for isolation and detection of viruses. Besides that, the system “cell culture-viruses” could be applied for different medical and biological aims. In the case, as an appropriate example has been characterized the application of cultivated avian pox viruses for production of rAPVs, expressing different antigens and hence – the possibility for using of such recombinants for therapy of different diseases by activation of the immune system. These recombinants could be used for such aims for birds, if the “parent” virus has been cultivated on avian CCs, and for mammals, including people, if the “parent” virus has been cultivated on mammalian CCs, respectively. APVs have been found to possess some advantages in comparison with vaccinia virus because of the abortive replication in mammalian cells and, hence, the possibility of less danger of pathogenesis. In in vitro- conditions, however, these viruses have been able to undergo the abortive replication in mammalian cells, and, in this way, they could be used for production for the pointed above biotechnological aims. Studies on the stem/progenitor cell biology are focused on their abilities for self-renewal and differentiation. These properties make them strong candidates for delivering of genes and restoring organ systems function, which have been established to be included in these processes. This idea has given rise to the notion that many aspects of the normal aging could primarily reflect limitations in DNA- repair and telomeric-maintenance pathways in the stem/progenitor cells of the soma. As a particular aim has been found the possibility for use of hematopoietic stem cells and/or of mesenchimal stem cells in various forms of cellular therapies, as well as genetic tools that can be used for a better understanding of the mechanisms leading to repair and regeneration of damaged and/or transformed cells. In this aspect, technique for preparing of cell vectors by transduction of genes in stem/progenitor cells, by virus gene constructions, has been established as a perspective for new therapeutic strategies.

References

  1. Al Haji M, Clarke M (2004) Self-renewal and solid tumor stem cells. Oncogene 23(43): 7274-7282.
  2. Lansdorp PJ (2005) Role of telomerase in hematopoietic stem cells. Ann NY Acad Sci 1044: 220- 227.
  3. Lansdorp PM (1995) Telomere length and proliferation potential of hematopoietic stem cells. Cell Sci 108(1): 1-6.
  4. Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3(7): 730-737.
  5. Kotobuki N, Hirose M, Takakura Y, Ongushi H (2004) Cultured autologous human cells for hard tissue regeneration: preparation and characterization of mesenchymal stem cells from bone marrow. Artif Organs 28(1): 33-39.
  6. Rattmann I, Klieff V, Feldmann A, Ludwig C, Sorg U, et al. (2007) Reliable generation of stable high titer producer cell lines for gene therapy. Intervirology 50(3): 197-203.
  7. Pommey S, Galipeau J (2006) The use of mesenchymal stromal cells in oncology and cell therapy. Bull Cancer 93(9): 901- 907.
  8. Sell S (2004) Stem cell origin of cancer and differentiation therapy. Crit Rev Oncol Hematol 51(1): 1-28.
  9. Terkikh A, Bryant P, Schwartz P (2006) Mammalian stem cells. Pediatric Research 59: 13-20.
  10. Pereboeva L, Komarova S, Mikheeva G, Krasnykh V, Curiel DT (2003) Approaches to utilize mesenchymal progenitor cells as cellular vehicles. Stem Cells 21(4): 389-404.
  11. Xu C, Inokuma MS, Denham J, Golds K, Kundu P, et al. (2001) Feeder-free growth of undifferentiated human embryonic stem cells. Nat Biotechnol 19(10): 971- 974.
  12. Bang FB, Levy E, Gey GO (1951) Some observations on host-cell-virus relationship in fowl pox. J Immunol 66(3): 329-345.
  13. Mayr A, Kalcher K (1960) Comparative studies on the propagation of pox viruses in tissue culture. Arch ges Virufirsh 10: 72-102.
  14. Chang W, Jasty V (1970) Multiplication of fowlpox virus in chicken embryo fibroblastic cell cultures. Amer J of Vet Res 31(8): 1463-1467.
  15. Hughes J, Sheridan J (1988) Enchanced production of poxvirus vectors by high speed rolling. Journal of Virological Methods 22(1): 75-80.
  16. Cox WI, Gettig RR, Paoletti E (1992) Poxviruses as genetic vectors. In: Vos JM (Edn.), Viruses in human gene therapy. New York, pp: 144-178.
  17. Sutter G, Moss B (1992) Non-replicating vaccinia vector efficiently expresses recombinant genes. Proc Natl Acad Sci 89(22): 10847-10851.
  18. Wang M, Bronte V, Chen PW, Gritz L, Panicali D, et al. (1995) Active immunotherapy of cancer with a nonreplicating recombinant fowlpox virus encoding a model tumor-associated antigen. J Immunol 154(9): 4685-4692.
  19. Zhai Y, Yang J, Kawakami Y, Spiess P, Wadsworth SC, et al. (1996) Antigen-specific tumor vaccines: development and characterization of recombinant adenoviruses encoding MART1 or gp100 for cancer therapy. J Immunol 156(2): 700-710.
  20. Palese P, Roizman B (1996) Genetic engineering of viruses and of virus vectors: a preface. Proc Natl Acad Sci 93(21): 11287.
  21. Parks R, Krell P, Derbyshire J, Nagy E (1994) Studies of fowlpox virus recombination in the generation of recombinant vaccines. Virus Research 32(3): 283- 297.
  22. Schirrmacher V (1995) Tumor vaccine design: concepts, mechanisms, and efficacy testing. Arch Allergy Immunol 108: 340-344.
  23. Karaka K, Sharma J, Wislow B, Junker DE, Reddy S, et al. (1998) Recombinant fowlpox viruses coexpressing chicken type I IFN and Newcastle disease virus HN and F genes: influence of IFN on protective efficacy and humoral responses of chickens following in ovo- or post-hatch administration of recombinant viruses. Vaccine 16(16): 1496-1503.
  24. Boyle D, Heine H (1993) Recombinant fowlpox virus vaccines for poultry. Immunology and Cell Biology 71: 391-397.
  25. Yu L, Liu W, Schnitzlein WM, Tripathy D, Kwang J (2001) Study of protection by recombinant fowl poxvirus expressing C-terminal nucleocapsid protein of infectious bronchitis virus against challenge. Avian Diseases 45(2): 340-348.
  26. Taylor J, Weinberg B, Languet B, Desmettre P, Paoletti E (1988) Recombinant fowlpox virus inducing protective immunity in non-avian species. Vaccine 6(6): 497-503.
  27. Paoletti E (1996) Application of poxvirus vectors to vaccination: an update. Proc Natl Acad Sci 93(21): 11349-11353.
  28. Boyle D (1992) Quantitive assessment of poxvirus promoters in fowlpox and vaccinia virus recombinants. Virus Genes 6(3): 281-290.
  29. Boyle D, Coupar B (1988) Construction of recombinant fowlpox viruses as vectors for poultry vaccines. Virus Research 10(4): 343-356.
  30. Wang M, Bronte V, Chen P, Gritz L, Panicali D, et al. (1995) Active immunotherapy of cancer with a nonreplicating recombinant fowlpox virus encoding a model tumor-associated antigen. J Immunol 154(9): 4685 - 4692.
  31. Rosenberg S (1996) The immunotherapy of solid cancers based on cloning the genes encoding tumor- rejection antigens. Ann Rev Med 47: 481-491.
  32. Kent S, Zhao A, Best S, Chandler J, Boyle D, et al. (1998) Enchanced T-cell immunogenecity and protective efficacy of a human immunodeficiency virus type 1 vaccine regimen consisting of consecutive priming with DNA and boosting with recombinant fowlpox virus. Journal of Virology 72(12): 10180-10188.
  33. Sedegah M, Weiss W, Sacci JB, Charoenvit Y, Hedstrom R, et al. (2000) Improving protective immunity induced by DNA-based immunization: priming with antigen and GM-CSF encoding plasmid DNA and boosting with antigen expressing recombinant poxvirus. J Immunol 164(11): 5905- 5912.
  34. Kauffman E, Bublot M, Gettig R, Limbach K, Pincus S, et al. (2001) Live viral vectors. In: Ronald Ellis W (Eds.), New Vaccine Technologies. Bio Chem Pharma, USA, pp: 303.
  35. Taylor J, Trimarchi C, Weinberg R, Languet B, Guillemin F, et al. (1991) Efficacy studies on a canarypoxrabies recombinant virus. Vaccine 9(3): 190-193.
  36. Roth J, Dittmer D, Rea D, Tartaglia J, Paoletti E, et al. (1996) p53 as a target for cancer vaccines: recombinant canarypox virus vectors expressing p53 protect mice against lethal tumor cell challange. PNAS USA 93(10): 4781-4786.
  37. Cadoz M, Steady A, Meignier B, Taylor J, Tartaglia J, et al. (1992) Immunization of man with canarypox virus expressing rabies glycoprotein. Lancet 339(8807): 1429-1432.
  38. Engelmayer J, Larsson M, Lee A, Lee M, Cox W, et al. (2001) Mature dendritic cells infected with canarypox virus elicit strong anti-human immunodeficiency virus CD8+ and CD4+ responses from chronically infected individuals. J Virol 75(5): 2142-2153.
  39. Schnitzlein W, Ghildial N, Tripathy D (1988) A rapid method for identifying the thymidine kinase genes of avipoxviruses. J Virol Methods 20: 341-352.
  40. Mackett M, Smith G, Moss B (1982) Vaccinia virus: a selectable eukaryotic cloning and expression vector. PNAS USA 79(23): 7415-7419.
  41. Moss B, Fields B, Knipe D, Howley P (1996) Poxviridae: the viruses and their replication. Virology 2(3): 2637-2701.
  42. Panicali D, Paoletti E (1982) Construction of poxviruses as cloning vectors: insertion of the thymidine kinase gene from herpes simplex virus into the DNA of infectious vaccinia virus. Proc Natl Acad Sci 79(16): 4927-4931.
  43. Spehner D, Drillen R, Lecocq JP (1990) Construction of fowlpox virus vectors with intergenic insertions: Expression of the β-galactosidase gene and the measles fusion protein. J Virol 64(2): 527-533.
  44. Galindo I, Lorenzo M, Blasco R (2001) Set of vectors for the expression of histidine-tagged proteins in vaccinia virus recombinants. Biotechniques 30(3): 524-526.
  45. Taylor J, Paoletti E (1988) Fowlpox virus as a vector in non-avian species. Vaccine 6(6): 466-468.
  46. Eo S, Gierynska M, Kamar A, Rouse B (2001) Prime- boost immunization with DNA vaccine: mucosal route of administration changes the rules. J Immunol 166(9): 5473-5479.
  47. Kumar S, Boyle D (1990) Mapping of a major early/late gene of fowlpox virus. Virus Res 15(2): 175- 185.
  48. Meldorf M (1997) Update of HIV vaccines. STEP Perspective, pp: 1-9.
  49. Boyle D, Coupar B, Gibbs A, Seigman L, Both G (1987) Fowlpox virus thymidine kinase: nucleotide sequence and relationships to other thymidine kinases. Virology 156(2): 355-365.
  50. Tjuvajev JG, Chen SH, Joshi A, Joshi R, Guo ZS, et al. (1999) Imaging adenoviral-mediated herpes virus thymidine kinase gene transfer and expression in vivo. Cancer Res 9(20): 5186-5193.
  51. Leong K, Ramsay A, Boyle D, Robinson H, Ramshaw I (1994) Novel vaccine strategies using fowlpox viruses and plasmid DNA. Ann Conf Australas Soc HIV Med 6(156): 3-6.
  52. Pfeiderer M, Falkner F, Dorner F (1995) A novel vaccinia virus expression system allowing construction of recombinants without the need for selection markers, plasmids and bacterial hosts. J Gen Virol 76(12): 2957-2962.
  53. Chun S, Daheshia M, Lee S, Rouse BT (1999) Immune modulation by IL-10 gene transfer via viral vector and plasmid DNA: implication for gene therapy. Cellular Immunology 194(2): 194-204.
  54. Domi A, Moss B (2005) Engineering of a vaccinia virus bacterial artificial chromosome in Escherichia coli by bacteriophage λ−based recombination. Nature Methods 2(2): 95-97.
  55. Somogyi P, Frazier J, Skinner M (1993) Fowlpox virus host range restriction: gene expression, DNA replication and morphogenesis in nonpermissive mammalian cells. Virology 197(1): 439-444.
  56. Simeonov K, Ivanov I, Popova T (2000) Propagation of avian pox vaccine strains in mammalian MDBK cell line. Macedonian Veterinary Review 29(2): 45-50.
  57. Sainova IV, Kril AI, Simeonov KB, Popova TP, Ivanov IG (2005) Investigation of the morphology of cell clones, derived from the mammalian EBTr cell line and their susceptibility to the vaccine avian poxvirus strains FK and Dessau. Journal of Virological Methods 127(1-2): 37-40.
  58. Landis S, Murray T, Bolden S, Wingo P (1999) Cancer statistics. CA Cancer J Clin 49(1): 8-31.
  59. Arthur J, Butterfield L, Roth MD, Bui LA, Kiertscher SM, et al. (1997) A comparison of gene transfer methods in human dendritic cells. Cancer Gene Ther 4(1): 1023-1028.
  60. WanY, Bramson J, Carter R, Graham F, Gauldie J (1997) Dendritic cells transduced with an adenoviral vector encoding a model tumor-associated antigen for tumor vaccination. Hum Gene Ther 8(11): 1355-1363.
  61. Todo T, Martuza RL, Rabkin SD, Johnson PA (2001) Oncolytic herpes simplex virus vector with enhanced MHC class I presentation and tumor cell killing. PNAS USA 98(11): 6396-6401.
  62. Tozola E, Hunt K, Swisher S, McBride W, Lau R, et al. (1996) In vivo-cancer gene therapy with a recombinant interleukin-2 adenovirus vector. Cancer Gene Ther 3(1): 17-25.
  63. Ezzele H, Balachandran S, Sicheri F, Poliak S, Barber G (2001) Analysing the mechanisms of interferon- induced apoptosis using CrmA and hepatitis C virus NS5A. Virology 281(1): 124-137.
  64. Gjersten M, Bakka A, Brevik J, Saeterdal I, Gedde Dahl T, et al. (1996) Ex vivo ras peptide vaccination in patients with advanced pancreatic cancer: results of a phase I/II study. Int J Cancer 65(4): 450-453.
  65. Davis NL, Brown KW, Johnson RE (1996) A viral vaccine vector that expresses foreign genes in lymph nodes and protects against mucosal challenge. J Virol 70(6): 3781-3787.
  66. Gong J, Chen L, Chen D, Kashiwaba M, Manome Y, et al. (1997) Induction of antigen-specific antitumor immunity with adenovirus-transduced dendritic cells. Gene Ther 4(10): 1023-1028.
  67. Kaplan J, Yu Q, Piraino S, Pennington SE, Shankara S, et al. (1999) Induction of antitumor immunity with dendritic cells transduced with adenovirus vector- encoding endogenous tumor-associated antigens. J Immun 163(2): 699-707.
  68. Borysievicz LK, Flander A, Numako M, Man S, Wilkinson GW, et al. (1996) A recombinant vaccinia virus encoding human papillomavirus types 16 and 18, E6 and E7 proteins as immunotherapy for cervical cancer. Lancet 347(9014): 1523-1527.
  69. Adams M, Borysiewics L, Fiander A, Man S, Jasani B, et al. (2001) Clinical studies of human papilloma vaccines in pre-invasive and invasive cancer. Vaccine 19(17-19): 3549-3556.
  70. Douglas JL, Lin WY, Panis ML, Veres G (2001) Efficient human immunodeficiency virus-based vector transduction of unstimulated human mobilized peripheral blood CD34+ cells in the SCID-hu Thy/Liv model of human T-cell lymphopoiesis. Hum Gene Ther 12(4): 401-413.
  71. Cordier L, Duffour M, Sabourin J, Lee MG, Cabannes J, et al. (1995) Complete recovery of mice from a pre- established tumor by direct intratumoral delivery of an adenovirus vector harboring the murine IL-12 gene. Gene Ther 2(1): 16-21.
  72. Gambotto A, Tuting T, McVey D, Kovesdi I, Tahara H, et al. (1999) Induction of antitumor immunity by direct intratumoral injection of a recombinant adenovirus vector expressing interleukin-12. Cancer Gene Ther 6(1): 45- 53.
  73. Tsang KY, Zaremba S, Nieroda CA, Zhu MZ, Hamilton JM, et al. (1995) Generation of human cytotoxicic T- cells specific for human carcinoembryonic antigen epitopes from patients immunized with recombinant vaccinia-CEA vaccine. J Natl Cancer Inst 87(13): 982- 990.
  74. Marshall JL, Hawkins MJ, Tsang KY, Richmond E, Pedicano JE, et al. (1999) Phase I study in cancer patients of a replication-defective avipox recombinant vaccine that expresses human carcinoembryonic antigen. J Clin Oncol 17(1): 332-337.
  75. Nanda D, de Jong M, Vogels R, Havenga M, Driesse M, et al. (2002) Imaging expression of adenoviral HSV1- tk suicide gene transfer using the nucleoside analogue FIRU. Eur J Nucl Med Mol Imaging 29(7): 939-947.
  76. Komarova S, Kawakami Y, Stoff Khalili MA, Curiel DT, Pereboeva L (2006) Mesenchymal progenitor cells as cellular vehicles for delivery of oncolytic adenoviruses. Mol Cancer Ther 5(3): 755 - 766.
  77. Okada T, Caplen NJ, Ramsey WJ, Onodera M, Shimazaki K, et al. (2004) In situ-generation of pseudotyped retroviral progeny by adenovirus- mediated transduction of tumor cells enhances the killing effect of HSV-tk suicide gene therapy in vitro and in vivo. J Gene Med 6(3): 288-299.
  78. Reiser J, Zhang XY, Hemenway CS, Mondal D, Pradhan L, et al. (2005) Potential of mesenchymal stem cells in gene therapy approaches for inherited and acquired diseases. Expert Opin Biol Ther 5(12): 1571-15784.
  79. Kashofer K, Bonnet D (2005) Gene therapy progress and prospects: stem cell plasticity. Gene Ther 12(16): 1229-1234.
  80. Xiong C, Tang D, Xie C, Zhang L, Xu K, et al. (2005) Stem cells and development: genetic engineering of human embryonic stem cells with lentiviral vectors. Neural Stem Cells Compendium 14(4): 367-377.
  81. Ballas C, Zielske S, Gerson S (2002) Adult bone marrow stem cells for cell and gene therapies: implications for greater use. Cell Biochem Suppl 38: 20-28.
  82. Robertson ES, Ooka T, Kieff ED (1996) Epstein-Barr virus vectors for gene delivery to B-lymphocytes. PNAS USA 93(21): 11384-11390.
  83. Zhang XY, La Russa V, Bao L, Kolls J, Schwarzenberger P, et al. (2002) Lentiviral vectors for sustained transgene expression in human bone marrow-derived stromal cells. Mol Ther 5(5): 555 - 565.
  84. Asano T, Hanazono Y, Ueda Y, Shin ichi M, Akihiro K, et al. (2002) Highly efficient gene transfer into primate embryonic stem cells with a simian lentivirus vector. Mol Ther 6(2): 162-168.
  85. Bovia F, Salmon P, Matthes T, Kvell K, Nguyen TH, et al. (2003) Efficient transduction of primary human B- lymphocytes and nondividing myeloma B-cells with HIV-1-derived lentiviral vectors. Blood 101(5): 1727- 1733.
  86. An DS, Wersto RP, Agricola BA, Metzger ME, Lu S, et al. (2000) Marking and gene expression by a lentivirus vector in transplanted human and nonhuman primate CD34(+) cells. J Virol 74(3): 1286- 1295.
  87. Choi JK, Hoang N, Vilardi AM, Conrad P, Emerson SG, et al. (2001) Hybrid HIV/MSCV LTR enhances transgene expression of lentiviral vectors in human CD34(+) hematopoietic cells. Stem Cells 19(3): 236- 246.
  88. Cui Y, Golob J, Kelleher E, Ye Z, Pardoll D, et al. (2002) Targeting transgene expression to antigen-presenting cells derived from lentivirus-transduced engrafting human hematopoietic stem/progenitor cells. Blood 99(2): 399-408.
  89. De Vos J, Bagnis C, Bonnafoux L, Requirand G, Jourdan M, et al. (2003) Comparison of murine leukemia virus, human immunodeficiency virus, and adeno- associated virus vectors for gene transfer in multiple myeloma: lentiviral vectors demonstrate a striking capacity to transduce low-proliferating primary tumor cells. Hum Gene Ther 14(18): 1727-1739.
  90. Haas DL, Case SS, Crooks GM, Kohn DB (2000) Critical factors influencing stable transduction of human CD34(+) cells with HIV-1-derived lentiviral vectors. Mol Ther 2(1): 71-80.
  91. Hamaguchi I, Woods NB, Panagopoulos I, Andersson E, Mikkola H, et al. (2000) Lentivirus vector gene expression during ES cell-derived hematopoietic development in vitro. J Virol 4(22): 10778-107784.
  92. Kosaka Y, Kobayashi N, Fukazawa T, Totsugawa T, Maruyama M, et al. (2004) Lentivirus-based gene delivery in mouse embryonic stem cells. Artif Organs 28(3): 271-277.
  93. Lotti F, Menguzzato E, Rossi C, Naldini L, Ailles L, et al. (2002) Transcriptional targeting of lentiviral vectors by long terminal repeat enhancer replacement. J Virol 76(8): 3996-4007.
  94. Mitta B, Rimann M, Ehrengruber MU, Ehrbar M, Djonov V, et al. (2002) Advanced modular self- inactivating lentiviral expression vectors for multigene interventions in mammalian cells and in vivo-transduction. Nucleic Acids Res 30(21): e113.
  95. Sirven A, Ravet E, Charneau P, Zennou V, Coulombel L, et al. (2001) Enhanced transgene expression in cord blood CD34(+)-derived hematopoietic cells, including developing T-cells and NOD/SCID mouse repopulating cells, following transduction with modified trip lentiviral vectors. Mol Ther 3(4): 438- 448.
  96. Salmon P, Oberholzer J, Occhiodoro T, Morel P, Lou J, et al. (2000) Reversible immortalization of human primary cells by lentivector-mediated transfer of specific genes. Mol Ther 2(4): 404-414.
  97. Barrette S, Douglas JL, Seidel NE, David Bodine M (2000) Lentivirus-based vectors transduce mouse hematopoietic stem cells with similar efficiency to moloney murine leukemia virus-based vectors. Blood 96: 3385-33891.
  98. Austin TW, Salimi S, Veres G, Morel F, Ilves H, et al. (2000) Long-term multilineage expression in peripheral blood from a Moloney murine leukemia virus vector after serial transplantation of transduced bone marrow cells. Blood 95(3): 829-836.
  99. Dorrell C, Gan OI, Pereira DS, Hawley RG, Dick JE (2000) Expansion of human cord blood CD34(+)CD38(-) cells in ex vivo-culture during retroviral transduction without a corresponding increase in SCID repopulating cell (SRC) frequency: dissociation of SRC phenotype and function. Blood 95(1): 102-110.
  100. Douglas J, Kelly P, Evans JT, Garcia JV (1999) Efficient transduction of human lymphocytes and CD34+ cells via human immunodeficiency virus- based gene transfer vectors. Hum Gene Ther 10(6): 935-945.
  101. Sutton RE, Wu HTM, Rigg R, Böhnlein E, Brown PO (1998) Human immunodeficiency virus type 1 vectors efficiently transduce human hematopoietic stem cells. J Virol 72(7): 5781-5788.
  102. Grande A, Piovani B, Aiuti A, Ottolenghi S, Mavilio F, et al. (1999) Transcriptional targeting of retroviral vectors to the erythroblastic progeny of transduced hematopoietic stem cells. Blood 93(10): 3276-3785.
  103. Hildinger M, Eckert HG, Schilz AJ, John J, Ostertag W, et al. (1998) FMEV vectors: both retroviral long terminal repeat and leader are important for high expression in transduced hematopoietic cells. Gene Ther 5(11): 1575- 1579.
  104. Kelly PF, Carrington J, Nathwani A, Vanin EF (2001) RD114-pseudotyped oncoretroviral vectors. Biological and physical properties. Ann N Y Acad Sci 938: 262-276.
  105. Kiem HP, Heyward S, Winkler A, Potter J, Allen JM, et al. (1997) Gene transfer into marrow repopulating cells: comparison between amphotropic and gibbon ape leukemia virus pseudotyped retroviral vectors in a competitive repopulation assay in baboons. Blood 90(11): 4638-4645.
  106. Klump H, Schiedlmeier B, Vogt B, Ryan M, Ostertag W, et al. (2001) Retroviral vector-mediated expression of HoxB4 in hematopoietic cells using a novel co-expression strategy. Gene Ther 8(10): 811- 817.
  107. Koch P, Siemen H, Biegler A, Itskovitz Eldor J, Brüstle O (2006) Transduction of human embryonic stem cells by ecotropic retroviral vectors. Nucleic Acids Research 34(18): e120.
  108. Koch S, Schwinger C, Kressler J, Heinzen Ch, Rainov NG (2003) Alginate encapsulation of genetically engineered mammalian cells: comparison of production devices, methods and microcapsule characteristics. J Microencapsul 20(3): 303-316.
  109. Bett AJ, Haddara W, Prevec L, Graham L (1994) An efficient and flexible system for construction of adenovirus vectors with insertions or deletions in early regions 1 and 3. PNAS USA 91(19): 8802-8806.
  110. Fallaux FJ, Bout A, van der Velde I (1998) New helper cells and matched early region 1-deleted adenovirus vectors prevent generation of replication-competent adenoviruses. Hum Gene Ther 9(13): 1909-1917.
  111. Zhang J, Hu C, Geng Y, Selm J, Klein SB, et al. (1996) Gene therapy with adeno-associated virus carrying an interferon gene results in tumor growth suppression and regression. Cancer Gene Ther 3(1): 31-38.
  112. Pramudji C, Shimura S, Ebara S, Yang G, Wang J, et al. (2001) In situ-prostate cancer gene therapy using a novel adenoviral vector regulated by the caveolin-1 promoter. Clin Cancer Res 7(12): 4272-4279.
More from this journal

Cite this article

BibTeX
APA
RIS
@article{iskra2019,
  title   = {Cultural Properties of Viruses and Design of Safe Recombinant Vaccines and Virus Gene Constructs on their Basis},
  author  = {Iskra V Sainova},
  journal = {Virology & Immunology Journal},
  year    = {2019},
  volume  = {3},
  number  = {4},
  doi     = {10.23880/vij-16000226}
}
Iskra V Sainova (2019). Cultural Properties of Viruses and Design of Safe Recombinant Vaccines and Virus Gene Constructs on their Basis. Virology & Immunology Journal, 3(4). https://doi.org/10.23880/vij-16000226
TY  - JOUR
TI  - Cultural Properties of Viruses and Design of Safe Recombinant Vaccines and Virus Gene Constructs on their Basis
AU  - Iskra V Sainova
JO  - Virology & Immunology Journal
PY  - 2019
VL  - 3
IS  - 4
DO  - 10.23880/vij-16000226
ER  -