Viral gene therapy |
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Authors: | Pablo Mancheño-Corvo Pilar Martín-Duque |
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Institution: | (1) Dpto. Biotecnologia, Universidad Francisco de Vitoria, Ctra. M-515. Pozuelo-Majadahonda, km.1,800. 28225 Pozuelo de Alarcón, Madrid, Spain |
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Abstract: | Cancer is a multigenic disorder involving mutations of both tumor suppressor genes and oncogenes. A large body of preclinical
data, however, has suggested that cancer growth can be arrested or reversed by treatment with gene transfer vectors that carry
a single growth inhibitory or pro-apoptotic gene or a gene that can recruit immune responses against the tumor.
Many of these gene transfer vectors are modified viruses. The ability for the delivery of therapeutic genes, made them desirable
for engineering virus vector systems. The viral vectors recently in laboratory and clinical use are based on RNA and DNA viruses
processing very different genomic structures and host ranges. Particular viruses have been selected as gene delivery vehicles
because of their capacities to carry foreign genes and their ability to efficiently deliver these genes associated with efficient
gene expression. These are the major reasons why viral vectors derived from retroviruses, adenovirus, adeno-associated virus,
herpesvirus and poxvirus are employed in more than 70% of clinical gene therapy trials worldwide. Because these vector systems
have unique advantages and limitations, each has applications for which it is best suited.
Retroviral vectors can permanently integrate into the genome of the infected cell, but require mitotic cell division for transduction.
Adenoviral vectors can efficiently deliver genes to a wide variety of dividing and nondividing cell types, but immune elimination
of infected cells often limits gene expressionin vivo. Herpes simplex virus can deliver large amounts of exogenous DNA; however, cytotoxicity and maintenance of transgene expression
remain as obstacles. AAV also infects many non-dividing and dividing cell types, but has a limited DNA capacity.
This review discusses current and emerging virus-based genetic engineering strategies for the delivery of therapeutic molecules
or several approaches for cancer treatment.
Supported by an unrestricted educational grant from AstraZeneca. |
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Keywords: | gene therapy virus adenovirus cancer |
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