Authors
Creative Biogene
Summary
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.
Introduction
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.
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