Efficient in Vivo Gene Expression by Trans - Splicing Adeno - Associated Viral Vectors  

Oleh:

Yi, Lai ; Yongping, Yue ; Mingju, Liu ; Ghosh, Arkasubhra ; Engelhardt, John F. ; Chamberlain, Jeffrey S. ; Dongsheng Duan

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Nature Biotechnology: The Science and Business of Biotechnology vol. 23 no. 11 (Nov. 2005), page 1435-1439.
Topik: vector; in vivo; gene expression; viral vectors

Ketersediaan

Perpustakaan Pusat (Semanggi) Nomor Panggil: NN9.4 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Although adeno associated virus (AAV) mediated gene therapy has been hindered by the small viral packaging capacity of the vector, trans-splicing AAV vectors are able to package twice the size of the vector genome. Unfortunately the efficiency of current trans-splicing vectors is very low. Here we show that rational design of the gene splitting site has a profound influence on trans splicing vector mediated gene expression. Using mRNA accumulation as a guide, we generated a set of efficient trans splicing vectors and achieved widespread expression of the 6-kb, h2-R19 mini-dystrophin gene in skeletal muscle of mix mice, a model for duchene muscular dystrophy. The dystrophic phenotype was ameliorated in both adult and aged mice. This demonstates the use of transplicing vectors to efficiently expresss a large therapeutic structural protein. This strategy should be applicable to other large therapeutic genes or large transcription regulatory elements.

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