Long term physiologic modification using rAAV in utero gene-therapyReport as inadecuate




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Genetic Vaccines and Therapy

, 2:4

First Online: 19 May 2004Received: 04 February 2004Accepted: 19 May 2004

Abstract

BackgroundTransfer of genes in utero via the amniotic fluid was shown previously with recombinant adeno-associated viruses rAAV to be highly efficient. Expression for over one year was demonstrated using reporter genes. In addition, it was shown previously that transgenes delivered by this method release protein into the general circulation. Given these results experiments were designed to test the hypothesis that in utero rAAV gene therapy could result in long term physiologic modification.

MethodsA rAAV recombinant expressing ciliary neurotrophic factor cntf and green fluorescent gfp in a polycistronic messenger was used to treat rat fetuses in utero. CNTF causes weight loss and decreased water consumption as a measurable physiologic effect. GFP was used as a marker of gene expression.

ResultsIn utero gene transfer with rAAV carrying human cntf and gfp resulted in long-term gene expression in rat. CNTF-specific physiologic effects of a decrease in weight and water intake were obtained. Expression of the GFP was documented in the treated animals at one year of age.

ConclusionGiven this data, in utero gene therapy with rAAV into multipotential stem cells resulted in long term systemic physiologic modification of the treated animals by the transgene product. In utero rAAV gene therapy potentially could be used for gene replacement therapy in metabolic disorders.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-0556-2-4 contains supplementary material, which is available to authorized users.

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Author: Deiadra J Garrett - J Craig Cohen - Janet E Larson

Source: https://link.springer.com/







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