Retrovirus Services

Retroviruses are RNA viruses which possess the unique ability to reverse transcribe their RNA genomes into a double-stranded DNA (proviral) intermediate, which can stably integrate into the genome of the host cell. This feature has been exploited in the development of vectors for therapeutic applications such as gene therapy of inherited diseases, where stable long-term integration of the gene is required. Besides, retrovirus vectors can infect a broad variety of cell types and have a relatively low toxicity profile when compared to the other virus vectors. As a result, they have been extensively represented in clinical trials. Lentiviruses such as human immunodeficiency virus type-1 (HIV-1) and Gamma retroviruses such as Moloney murine leukemia virus (MMLV) have been used extensively in the engineering of derivative viral vectors.

Retroviral vectors (RVs) have been widely used to deliver therapeutic genes in the context of gene therapy (GT) clinical applications for cancer, monogenic disorders, and infectious diseases providing the stable and efficient expression of the transgene to patients. The first clinical gene therapy trial was designed to correct the inherited deficiency of the enzyme adenosine deaminase (ADA) by retroviral vector-mediated transfer of the ADA gene to hematopoietic cells ex vivo. ADA deficiency affects primarily lymphocytes and results in SCID. Therefore, lymphoid cells transduced with an ADA-expressing vector might survive and proliferate better than their nontransduced counterparts. A review of clinical trials on ex vivo gene therapy for ADA deficiency including more than 30 patients since the year 2000 concluded that the therapy had been successful and safe. Other protocols aiming at correcting inherited monogenic disorders, such as thalassemia, X-Linked adrenoleukodystrophy and the X-SCID by stable ex vivo gene transfer into hematopoietic cells, use either retro- or lentiviral vectors.

 Retroviruses in human gene therapy.

Figure 1. Retroviruses in human gene therapy.

Retroviruses have received attention as transfer vehicles in human gene therapy protocols, particularly in cases where stable maintenance and expression of the transferred gene is needed. In fact, all retroviral vector systems approved for clinical trials are based on single-cycle vector transfer from a specialized packaging cell that delivers the necessary viral proteins. Improvements of this basic technology have addressed questions of safety, especially by minimizing the risk for the generation of RCVs by recombination as well as questions of efficacy by optimizing all components and protocols.

Through QVirus™ platform, Creative Biogene can provide customized, standardized, and reliable and high-quality retroviral vector services and products to accelerate your human gene therapy studies. Our service covers all aspects from virus engineering, virus validation to cell biology. Besides, various types of retroviral vector systems have been established in-house to facilitate oncolytic virus development with a reduced budget and less time. If you have any special requirements, please feel free to contact us.

References
1. Pedersen F S, Duch M. Retroviruses in Human Gene Therapy[M]// eLS. John Wiley & Sons, Ltd, 2014.
2. Cooray S, et al. Retrovirus and Lentivirus Vector Design and Methods of Cell Conditioning. Methods in enzymology, 2012, 507:29-57.

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