Gene therapy with adeno-associated viral (AAV) vectors has reached the clinical stage for many inherited and acquired diseases. However, due to a cargo capacity limited to <5 kb, AAV-mediated treatment of diseases that require transfer of larger genes still appears elusive. This is a major drawback of a platform that has otherwise been repeatedly found to be safe and effective. Thus, great efforts have been directed toward the identification of strategies to overcome this limitation. Among the most studied approaches is the use of dual vectors, in which a transgene is split across two separate AAV vectors. Mechanisms acting at either the DNA, pre-mRNA, or protein levels have been explored to restore full-length transgene expression in infected cells. Here, we will review them as well as additional strategies developed to deliver large genes with AAV. We discuss the pros and cons of these strategies and the aspects that still need to be addressed.

Can Adeno-Associated Viral Vectors Deliver Effectively Large Genes? / Tornabene, P; Trapani, I. - In: HUMAN GENE THERAPY. - ISSN 1557-7422. - 31:1-2(2020), pp. 47-56. [10.1089/hum.2019.220]

Can Adeno-Associated Viral Vectors Deliver Effectively Large Genes?

Tornabene P;Trapani I
2020

Abstract

Gene therapy with adeno-associated viral (AAV) vectors has reached the clinical stage for many inherited and acquired diseases. However, due to a cargo capacity limited to <5 kb, AAV-mediated treatment of diseases that require transfer of larger genes still appears elusive. This is a major drawback of a platform that has otherwise been repeatedly found to be safe and effective. Thus, great efforts have been directed toward the identification of strategies to overcome this limitation. Among the most studied approaches is the use of dual vectors, in which a transgene is split across two separate AAV vectors. Mechanisms acting at either the DNA, pre-mRNA, or protein levels have been explored to restore full-length transgene expression in infected cells. Here, we will review them as well as additional strategies developed to deliver large genes with AAV. We discuss the pros and cons of these strategies and the aspects that still need to be addressed.
2020
Can Adeno-Associated Viral Vectors Deliver Effectively Large Genes? / Tornabene, P; Trapani, I. - In: HUMAN GENE THERAPY. - ISSN 1557-7422. - 31:1-2(2020), pp. 47-56. [10.1089/hum.2019.220]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/939428
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