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[摘要]：HSV-1 is a neurotropic virus that displays several important adaptations to the nervous system of the host organism, each of which can be rationally exploited in the design of gene therapy vectors for neurological applications. Replication-incompetent (replication-defective) helper-independent recombinant vectors are nontoxic tools for gene transfer that preserve most of the neurotropic features of HSV-1, particularly the ability to express genes after establishing latent infections, and are thus proficient candidates for therapeutic gene transfer in neurons. A clinical trial with the use of a replication-incompetent vector, NP-2 (Diamyd Inc), for the treatment of pain has been initiated. Attenuated replication-competent (oncolytic) vectors are becoming suitable and powerful tools to eradicate brain tumors, such as malignant gliomas, as a result of the ability to replicate and spread only within the tumor mass. Some attenuated replication-competent vectors, such as G-207 and HSV-1716 (Crusade Laboratories Ltd), have been used in clinical trials for the treatment of cancers including recurrent malignant glioma. Helper-dependent amplicon vector technology takes advantage of the capacity of the virus particle to accommodate <= 150 Kbp of foreign DNA, enabling these vectors to deliver complete genomic loci to the nucleus of mammalian cells, making amplicons particularly useful agents in protocols that require stable and physiological transgene expression. However, difficulties in obtaining large stocks of helper-free amplicons continue to limit the use of these vectors in the clinic. |
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