Vectors derived from herpes simplex virus provide a mean of gene delivery to neurons. The virus is readily taken up at nerve terminal, passes by rapid retrograde transport within neurons, and is selectively transferred across synapses, thus allowing its entrance from the periphery into the brain. This virus can enter a state of latency in some neurons, where it exists as an episomal element in the nucleus and is transcriptionally active to a reduced extent. In this state, the virus is apparently benign and can affect stable expression of foreign genes. The large genome (152 kb) can accommodate at least 50 kb of foreign DNA. Through mutations and deletions in the viral genome of specific HSV-1 strains it is possible to abolish the toxicity of the virus and reduce or eliminate its ability to replicate within neurons. Homologous, heterologous and tissue specific promoters will allow high expression of the gene interested in the nervous system. These vectors may be a useful tool to deliver...
Gene therapy of the nervous system by herpes virus vectors
MANSERVIGI, Roberto;ARGNANI, Rafaela;ZUCCHINI, Silvia;
1997
Abstract
Vectors derived from herpes simplex virus provide a mean of gene delivery to neurons. The virus is readily taken up at nerve terminal, passes by rapid retrograde transport within neurons, and is selectively transferred across synapses, thus allowing its entrance from the periphery into the brain. This virus can enter a state of latency in some neurons, where it exists as an episomal element in the nucleus and is transcriptionally active to a reduced extent. In this state, the virus is apparently benign and can affect stable expression of foreign genes. The large genome (152 kb) can accommodate at least 50 kb of foreign DNA. Through mutations and deletions in the viral genome of specific HSV-1 strains it is possible to abolish the toxicity of the virus and reduce or eliminate its ability to replicate within neurons. Homologous, heterologous and tissue specific promoters will allow high expression of the gene interested in the nervous system. These vectors may be a useful tool to deliver...I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
