Abstract
Adeno-associated virus (AAV) vectors are derived from the non-pathogenic parvovirus. The genome of AAV vector does not integrate into the host chromosome and persists as an episome in the nucleus of host cells. Although their small packaging capacity (about 3 kb) can limit the use of AAV vectors, most therapeutic genes fall within this size range. Use of multiple vectors and simultaneous expression of the respective genes into the target cell can overcome this drawback. AAV vectors transduce neurons efficiently and can express therapeutic genes or miRNA for prolonged periods without causing any toxic effects. To date, AAV vectors have been used in more than 183 clinical trials conducted for various diseases such as retinal degeneration, hemophilia, and Parkinson disease, and have shown no adverse effects. The expression of dopamine-synthesizing enzymes persisted 15 years after gene transfer in a primate model of Parkinson’s disease. In clinical studies, intraputaminal delivery of AAV vectors that contain aromatic l-amino acid decarboxylase (AADC) gene show the beneficial effects in patients with either advanced Parkinson’s disease or AADC deficiency. Some AAV vectors can cross the blood or cerebrospinal fluid-brain barrier and transduce neurons of the central nervous system after systemic injection. Use of these AAV vectors in proof-of-principle investigations of animal models for various metabolic and neurologic diseases such as lysosomal storage disease, Alzheimer’s disease, spinocerebellar ataxia, and motor neuron disease has yielded favorable results. Various advantages of AAV vector-based gene therapy compared to ordinary drugs necessitate the development of more manufacturing systems that can optimize large-scale production of GMP-grade AAV vectors.
Published Version
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