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Review

Riboswitches for Controlled Expression of Therapeutic Transgenes Delivered by Adeno-Associated Viral Vectors

1
Department of Immunology and Microbiology, the Scripps Research Institute, Jupiter, FL 33458, USA
2
Emmune, Inc., Jupiter, FL 33458, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Cristina Romero-López and Alfredo Berzal-Herranz
Pharmaceuticals 2021, 14(6), 554; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060554
Received: 9 May 2021 / Revised: 28 May 2021 / Accepted: 4 June 2021 / Published: 10 June 2021
(This article belongs to the Special Issue Potential of the Aptamers to Fill Therapeutic and Diagnostic Gaps)
Vectors developed from adeno-associated virus (AAV) are powerful tools for in vivo transgene delivery in both humans and animal models, and several AAV-delivered gene therapies are currently approved for clinical use. However, AAV-mediated gene therapy still faces several challenges, including limited vector packaging capacity and the need for a safe, effective method for controlling transgene expression during and after delivery. Riboswitches, RNA elements which control gene expression in response to ligand binding, are attractive candidates for regulating expression of AAV-delivered transgene therapeutics because of their small genomic footprints and non-immunogenicity compared to protein-based expression control systems. In addition, the ligand-sensing aptamer domains of many riboswitches can be exchanged in a modular fashion to allow regulation by a variety of small molecules, proteins, and oligonucleotides. Riboswitches have been used to regulate AAV-delivered transgene therapeutics in animal models, and recently developed screening and selection methods allow rapid isolation of riboswitches with novel ligands and improved performance in mammalian cells. This review discusses the advantages of riboswitches in the context of AAV-delivered gene therapy, the subsets of riboswitch mechanisms which have been shown to function in human cells and animal models, recent progress in riboswitch isolation and optimization, and several examples of AAV-delivered therapeutic systems which might be improved by riboswitch regulation. View Full-Text
Keywords: adeno-associated virus; gene therapy; transgene; aptamer; riboswitch; ribozyme; aptazyme; gene expression control; gene regulation adeno-associated virus; gene therapy; transgene; aptamer; riboswitch; ribozyme; aptazyme; gene expression control; gene regulation
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MDPI and ACS Style

Tickner, Z.J.; Farzan, M. Riboswitches for Controlled Expression of Therapeutic Transgenes Delivered by Adeno-Associated Viral Vectors. Pharmaceuticals 2021, 14, 554. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060554

AMA Style

Tickner ZJ, Farzan M. Riboswitches for Controlled Expression of Therapeutic Transgenes Delivered by Adeno-Associated Viral Vectors. Pharmaceuticals. 2021; 14(6):554. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060554

Chicago/Turabian Style

Tickner, Zachary J., and Michael Farzan. 2021. "Riboswitches for Controlled Expression of Therapeutic Transgenes Delivered by Adeno-Associated Viral Vectors" Pharmaceuticals 14, no. 6: 554. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060554

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