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Gene Therapy and Regulation , Vol. 2, No. 4, pp. 369 – 387 (2004) VSP 2004. Also available online - www.vsppub.com Safe delivery of therapeutic genes into specific chromosomal sites using engineered retroviral integrase ∗ THOMAS A. WILKINSON, WENJIE TAN and SAMSON A. CHOW † Department of Molecular and Medical Pharmacology, Molecular Biology Institute, and UCLA AIDS Institute, UCLA School of Medicine, Los Angeles, CA 90095, USA Received 16 March 2005; revised 31 March 2005 Abstract —Gene therapy approaches that involve the permanent insertion of therapeutic genes into host chromosomal DNA have many desirable features and show considerable promise for success in the clinic. One major drawback of these approaches is that any unintended insertion events from the therapy can potentially have detrimental effects in patients, as demonstrated by the development of malignancies in both animal and human studies. Therefore, directing the integration of foreign genes into “safe sites” within the genome is highly desirable for these approaches. In retroviral-based vector systems, the viral enzyme integrase (IN) catalyzes the insertion of a desired transgene nonspecifically into the host cell genome. Efforts to engineer IN to recognize specific target DNA sequences within the genome, and thereby improve the
Gene Therapy and Regulation – Brill
Published: Jan 1, 2004
Keywords: ZINC-FINGER PROTEIN; INTEGRASE; SITE-SPECIFIC INTEGRATION; HUMAN IMMUNODEFICIENCY VIRUS; GENE THERAPY
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