Chemistry of Life

Molecular genetics, biochemistry

targetted genetic repair

Targeted genetic repair: an emerging approach to genetic therapy -- Sullenger 112 (3): 310 -- Journal of Clinical Investigation: "Targeted gene repair is a powerful yet controversial technique developed to direct base changes in chromosomal genes, while RNA repair is an emerging strategy to alter the coding content of messenger RNAs.

Genetic repair strategies may have significant therapeutic and safety advantages over traditional gene therapy approaches for the treatment of many genetic disorders. Firstly, because the mutant genetic instructions are directly repaired, the corrected RNAs and/or DNAs will be maintained in their native sequence context and be regulated by their endogenous regulatory machinery. Secondly, in the instance where the mutant gene encodes a deleterious or dominant-negative mutant protein, repair of the mutant should simultaneously engender the regulated production of the wild-type protein while eliminating or reducing expression of the deleterious gene product. Finally, genetic repair strategies attempt to repair defective instructions in a site-specific manner. Therefore, once adequately developed, these strategies will result in less random mutagenesis of the genome and lead to fewer mutagenic side effects than do methods that randomly insert genes into the genome. "
J. Clin. Invest. 112:310-311 (2003). doi:10.1172/JCI200319419. Perspective : Targeted genetic repair: an emerging approach to genetic therapy

Related Free Full Text articles:
Hacein-Bey-Abina, S. et al.2003. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N. Engl. J. Med. 348:193-194.[Free Full Text]
Long, M.B., Jones, J.P. III, Sullenger, B.A., and Byun, J. 2003. Ribozyme-mediated revision of RNA and DNA. J. Clin. Invest. 112:312-318. doi:10.1172/JCI200319386.[Free Full Text]
Lan, N. et al.1998. Ribozyme-mediated repair of sickle ß-globin mRNAs in erythrocyte precursors. Science. 280:1593-1596.[Abstract/Free Full Text]
Watanabe, T., and Sullenger, B.A. 2000. Induction of wild-type p53 activity in human cancer cells by ribozymes that repair mutant p53 transcripts. Proc. Natl. Acad. Sci. U. S. A. 97:8490-8494.[Abstract/Free Full Text]
Rogers, C.S., Vanoye, C.G., Sullenger, B.A., and George, A.L. 2002. Functional repair of a mutant chloride channel using a trans-splicing ribozyme. J. Clin. Invest. 110:1783-1789. doi:10.1172/JCI200216481.[Abstract/Free Full Text]
Broitman, S., Amosova, O., Dolinnaya, N.G., and Fresco, J.R. 1999. Repairing the sickle cell mutation. I. Specific covalent binding of a photoreactive third strand to the mutated base pair. J. Biol. Chem. 274:21763-21768.[Abstract/Free Full Text]
Vasquez, K.M., Narayanan, L., and Glazer, P.M. 2000. Specific mutations induced by triplex-forming oligonucleotides in mice. Science. 290:530-533.[Abstract/Free Full Text]

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