Dual and triple AAV approaches are options for circumventing this drawback however they rely on co-transduction of multiple viral particles in the same cell, and on efficient intracellular recombination of the viral DNA or expressed proteins 9, 10, 11.Ī less common approach is to use rational protein design to generate shortened versions of the protein of interest. Elements such as promoters, polyadenylation sequences, and other regulatory elements further limit the size of transgenes that can be packaged. However AAVs remain limited by their capsid packaging capacity, which only allows transport of ~5 kb of genetic material. Capsid design and discovery efforts have dramatically improved AAV transduction rates, particularly in neuronal tissues 1, 2, 3, 4, 5, 6, 7, 8. Furthermore, various AAV serotypes and variants display broad but distinct tropisms that allow targeting to specific cell types 4, 5, 6, 7. Their low toxicity and immunogenicity minimize adverse reactions and they produce long-term transgene expression. Advances in gene therapy have positioned adeno-associated viruses (AAV) as a ubiquitous delivery tool for treating monogenic inherited disorders 1, 2, 3.
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