Gammaretroviral and lentiviral vectors for gene therapy have been developed that mediate stable genetic modification of treated cells by chromosomal integration of the transferred vector genomes. This is highly desired, not only for research use, but also for clinical gene therapy aiming at the long-term correction of genetic defects, e.g., in stem and progenitor cells.

Retroviral vector particles with tropism for various target cells have been designed. Due to split genome vector design the risk of replication-competent retrovirus formation has been minimized. Gammaretroviral and lentiviral vectors have so far been used in more than 300 clinical trials, addressing treatment options for various diseases. In some cases these trials resulted in benefit for treated patients suffering from life threatening disease.

Insertional mutagenesis due to vector integration in or next to cellular proto-oncogenes was concluded to be necessary for the lymphoproliferative disease observed in some patients treated with gammaretrovirally modified haematopoietic stem cells for X-linked severe combined immunodeficiency disease. These findings prompted the design of gammaretroviral vectors harbouring self-inactivating (SIN) Long Terminal Repeats (LTRs), which current lentiviral vectors already have.

SIN vectors may reduce the effect of insertional mutagenesis and proto-oncogene activation, thereby reducing the risk of oncogenesis. With a view to future clinical use, new developments such as cell entry targeting will further improve the safety and efficacy of retroviral vectors.

Further reading:
Retroviruses: Molecular Biology, Genomics and Pathogenesis
Lentiviruses and Macrophages: Molecular and Cellular Interactions

Labels: Lentiviral, lentivirus, lentiviruses, Retroviral vectors, Vectors for Gene Delivery

Retroviruses comprise a diverse family of enveloped RNA viruses, remarkable for their use of reverse transcription of viral RNA into linear double stranded DNA during replication and the subsequent integration of this DNA into the genome of the host cell. Members of this family include important pathogens such as HIV-1, feline leukemia, and several cancer-causing viruses.

Research into retroviruses led to the discovery of oncogenes, a major advance in the field of cancer genetics. Studies of retroviruses have contributed greatly to our understanding of mechanisms that regulate eukaryotic gene expression.

Retroviruses are proving to be valuable research tools in molecular biology and have been used successfully in gene therapy (e.g. to treat X-linked severe combined immunodeficiency).

Further reading: Retroviruses: Molecular Biology, Genomics and Pathogenesis

Labels: Lentiviral, lentivirus, lentiviruses, Retroviral, Retrovirus, retroviruses