LENTIVIRAL VECTORS. introduction. Lenti - latent-slow Retroviridae Enveloped , spherical viruses with a genome size of ~ 8kb Can replicate in the non dividing cells-making them one of the most efficient gene delivery vector
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Enveloped , spherical viruses with a genome size of ~ 8kb
Can replicate in the non dividing cells-making them one of the most efficient gene delivery vector
Although transmission is generally via infectious particles, lentiviruses are capable of infecting neighboring cells in direct contact with the host cells, without having to form extracellular particles.
Human Immunodeficiency Virus 1 and 2
Simian Immunodeficiency Virus
Feline Immunodeficiency Virus
Bovine immunodeficiency virus
Equine infectious anemia virus
Caprine encephalitis virus
HOW TO MAKE A VIRAL VECTOR FROM THE VIRUS?
The steps involved
NO HELPER VIRUS- NO GOI!
THE PROBLEM-GENETIC RECOMBINATION!
Vaccines currently available
Lentiviruseshave a high mutation rate due to low fidelity of the lentivirusreverse transcriptase and the absence of proofreading activity. This results in the constant generation of mutants that escape from surveillance either by antibodies or specific T -cells.
Following integration of the proviral DNA into the host genome lentiviruses can remain in a quiescent state, invisible for the immune system. The initial site of infection is usually at the mucosae of the genital tracts or the intestine where the virus can replicate in the dendritic cells.
To limit viral replication in this initial stage of infection the induction of an effective mucosal immune response will be necessary. Unfortunately most vaccine strategies pursued currently do not induce mucosal immune responses.
Another problem in the immunologic control of lentivirus infection is that they destroy or interfere with the functioning of T helper cells which have a key role in the immune system.