Evolution and containment of transmissible recombinant vector vaccines
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Transmissible vaccines offer a revolutionary approach for controlling infectious disease and may provide one of the few feasible methods for eliminating pathogens from inaccessible wildlife populations. Current efforts to develop transmissible vaccines use recombinant vector technology whereby pathogen antigens are engineered to be expressed from innocuous infectious viral vectors. The resulting vaccines can transmit from host to host, amplifying the number of vaccine-protected individuals beyond those initially vaccinated directly through parenteral inoculation. One main engineering challenge is the potential for natural selection to favor vaccine mutants that eliminate or reduce expression of antigenic inserts, resulting in immunogenic decay of the vaccine over time. Here, we study a mathematical model of vector mutation whereby continuous elimination of the antigenic insert results in reversion of the vaccine back into the insert-free vector. We use this model to quantify the maximum allowable rate of reversion that can be tolerated for a transmissible vaccine to maintain a critical threshold level of immunogenicity against a target pathogen. Our results demonstrate that even for transmissible vaccines where reversion is frequent, performance will often substantially exceed that of conventional, directly administered vaccines. Further, our results demonstrate the feasibility of designing transmissible vaccines that yield desired levels of immunogenicity, yet degrade at a rate sufficient for persistence of the recombinant vaccine within the environment to be minimized.Cite
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The vectors of gene therapy include viral vector and nonviral vector. For the problems of the safety of viral vector, at present, the research of nonviral vector is important. Nonviral vectors is a newly gene delivery system which has lower-toxicant,less immune reactions, lower probability of gene integration, and non-limitation of gene insertion clip size,it also has other characteristics such as the convenience of the use and preparation, easy conservation and probation. As a normal nonviral vector, liposome was easily to be prepared and has high safety to be preserved, but it was so hardly to get the requirement of quality control. For the lower efficiency of gene delivery in vivo and problems of target, its application was limited. The research of pH-sensitive liposome and positive ion liposome increase the efficiency of delivery of liposome. And the application of the high polymer carriers and nanoparticle in the gene therapy has open up a vast range of prospects for making use of nonviral vector in clinical practice.
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Transduction (biophysics)
Gene transfer
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Gene transfer
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Recombinant viral vectors have been developed for use as therapeutic agents and for the introduction of exogenous genes into living cells. However, little is known about the viability and stability of such recombinant viruses during storage, transport and delivery under various conditions. We describe here an analysis of the stability of an adenoviral vector in crude solutions of cell lysates during freezing and thawing and during storage at various temperatures in the presence and in the absence of glycerol. For example, the titer of adenoviruses in crude lysates of infected cells was reduced only ten‐fold or three‐fold after two hundred rounds of freezing and thawing or after incubation at 28°C for 14 days, respectively. Our observations indicate that recombinant adenoviral vector was more stable than expected both during freezing and thawing and during storage at low temperatures. Our results confirm the importance of appropriate conditions for the delivery and transport of recombinant adenoviral vectors.
Recombinant virus
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Objective To construct the recombinant adenovirus carrying hpapss1 cDNA and overexpress PAPSS1 in macrophages. Methods The full length of hpapss1 cDNA was amplified and cloned into eukaryotic expression vector pCDNA3.0 (pCDNA3.0-hpapss1). The segment of hpapss1 was subcloned into the shuttle plasmid pshuttle-CMV (pshuttle-CMV-hpapss1). The homologous recombination of pshuttle-CMV-hpapss1 and the backbone plasmid pAdEasy-1 took place in the E.coli BJ5183,and then the recombinant adenoviral plasmid (pAdEasy-1-hpapss1) was generated. The identified adenovirus vector was transfected into 293 cells to pack and amplify the adenovirus. The viral titer was checked by adenovirus plaque assay. Overxepression of PAPSS1 in THP-1 derived macrophages infected with Ad-hpapss1 for 48h was determined by Western blot. Results The recombinant adenovirus carrying hpapss1 was constructed successfully. The viral titer was 5.3×108 pfu/mL. The recombinant adenovirus could introduce hpapss1 into macrophages. Conclusions The recombinant adenovirus carrying hpapss1 would be a good model to study the effect of PAPSS1 and oxysterol sulfation on cholesterol metabolism.
Shuttle vector
HEK 293 cells
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The viral vector is an ideal tool for cell genetic modification in biomedical research and gene therapy. It is one of the hotspots in the research of genetic engineering. The vector is a transportation tool for inserting and transferring the target gene into the host cell. The virus vector could cure incurable diseases and explore the safety of the viral vector and toxic problems. At present, more researches are retrovirus, lentivirus, adenovirus, adeno-associated virus vector system. In this review, application and development of the above four viral vectors in neural stem cell were reviewed.
Key words:
Viral vector; Gene therapy; Neural stem cells; Application
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Objective To construct the adenovirus vector carrying the recombinant human hypoxia-inducible factor-1 and amplify the adenovirus vector in 293 cells. Methods The recombinant human HIF-1α gene was obtained from constructed plasmid pc-DNA4-rhHIF-1α by RT-PCR and then inserted into linearized pEGFP-C1 plasmid.The EGFP-rhHIF-1α gene segment was amplified by RT-PCR from pEGFP-rhHIF-1α vector and cloned into the plasmid PUC18.After having been screened,the constructed pUC18-EGFP-rhHIF-1α plasmid was digested with restriction endonucleases and cloned into the shuttle plasmid PDC316 to form PDC316-rhHIF-1α vector.The PDC316-rhHIF-1α plasmid was cotransfected with genomic plasmid pBHGloxΔ1,3Cre into 293 cells to package the recombinant adenovirus.The recombinant adenovirus was transfected into SG-7901 cells,and the green fluorescence protein expression was detected. Results Recombinant adenoviral vector Ad-rhHIF-1α was constructed successfully,and confirmed by restriction enzyme digestion and GFP expression. Conclusion The recombinant adenoviral vector carrying rhHIF-1α can be successfully constructed.
HEK 293 cells
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Cancer gene therapy is the transfer of genetic material to the cells of host with the goal of eradicating cancer cells,both in the primary tumor and metastases. Therapeutic agents in cancer gene therapy are delivered to the tumor cell using a carrier that might be either a nonviral vector or,the more efficient at gene delivery to target cells,a viral vector. It contains adenoviral vectors,adeno-associated virus vectors,retroviral vectors and herpes viral vectors,which have been widely used in basic research and clinical trials.
Adeno-associated virus
Gene transfer
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Despite the extensive research efforts over the past 25 years that have focused on HIV, there is still no cure for AIDS. However, tremendous progress in the understanding of the structure and biology of the HIV virus led to the development of safe and potent HIV-based transgene delivery vectors. These genetic vehicles are referred to as lentiviral vectors. They appear to be better suited for particular applications, such as transgene delivery into stem cells, compared to other viral- and non-viral vectors. This is because Lentivirus-based vectors can efficiently infect nondividing and slowly dividing cells. In the present review article, the current state of understanding of HIV-1 is discussed and the main characteristics that had an impact on vector design are outlined. A historical view on the vector concept is presented to facilitate discussion of recent results in vector engineering in a broader context. Subsequently, a state of the art overview concerning vector construction and vector production is given. This review also touches upon the subject of lentiviral vector safety and related topics that can be helpful in addressing this issue are discussed. Finally, examples of Lentivirus-based gene delivery systems and their applications are presented, with emphasis on animal transgenesis and human gene therapy.
Gene transfer
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