Therapeutic application of chimeric RNA/DNA oligonucleotide based gene therapy.

ABSTRACT

Chimeric RNA/DNA oligonucleotides, or chimera, have emerged as a breakthrough technology for treating genetic disorders. Chimera have been shown to induce correction of point mutations in several genetic disease models without utilising the viral vectors. Recent studies of chimera-based gene therapy in genetic disease models are reviewed. Chimera were delivered intravenously, intramuscularly, intradermally, or topically with or without vehicles. Correction of the mutation at genotypic and phenotypic levels was assessed using various methods. The gene correction frequency varied, ranging from 1-40%. The resulting phenotype changes lasted longer than one year in some studies. The most dramatic phenotypic change is the reduction of serum bilirubin level by 50% in the Gunn rat, a model for Crigler-Najjar syndrome. Chimera based gene therapy has the potential to develop into powerful therapeutic modality for genetic diseases.