Riboswitches for Controlled Expression of Therapeutic Transgenes Delivered by Adeno-Associated Viral Vectors
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 limit...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-06-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/14/6/554 |
| _version_ | 1797530554278608896 |
|---|---|
| author | Zachary J. Tickner Michael Farzan |
| author_facet | Zachary J. Tickner Michael Farzan |
| author_sort | Zachary J. Tickner |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T10:31:40Z |
| format | Article |
| id | doaj.art-cc9ed09dfd344d08a7d369d05b5b6d91 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T10:31:40Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-cc9ed09dfd344d08a7d369d05b5b6d912023-11-21T23:39:04ZengMDPI AGPharmaceuticals1424-82472021-06-0114655410.3390/ph14060554Riboswitches for Controlled Expression of Therapeutic Transgenes Delivered by Adeno-Associated Viral VectorsZachary J. Tickner0Michael Farzan1Department of Immunology and Microbiology, the Scripps Research Institute, Jupiter, FL 33458, USADepartment of Immunology and Microbiology, the Scripps Research Institute, Jupiter, FL 33458, USAVectors 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.https://www.mdpi.com/1424-8247/14/6/554adeno-associated virusgene therapytransgeneaptamerriboswitchribozyme |
| spellingShingle | Zachary J. Tickner Michael Farzan Riboswitches for Controlled Expression of Therapeutic Transgenes Delivered by Adeno-Associated Viral Vectors Pharmaceuticals adeno-associated virus gene therapy transgene aptamer riboswitch ribozyme |
| title | Riboswitches for Controlled Expression of Therapeutic Transgenes Delivered by Adeno-Associated Viral Vectors |
| title_full | Riboswitches for Controlled Expression of Therapeutic Transgenes Delivered by Adeno-Associated Viral Vectors |
| title_fullStr | Riboswitches for Controlled Expression of Therapeutic Transgenes Delivered by Adeno-Associated Viral Vectors |
| title_full_unstemmed | Riboswitches for Controlled Expression of Therapeutic Transgenes Delivered by Adeno-Associated Viral Vectors |
| title_short | Riboswitches for Controlled Expression of Therapeutic Transgenes Delivered by Adeno-Associated Viral Vectors |
| title_sort | riboswitches for controlled expression of therapeutic transgenes delivered by adeno associated viral vectors |
| topic | adeno-associated virus gene therapy transgene aptamer riboswitch ribozyme |
| url | https://www.mdpi.com/1424-8247/14/6/554 |
| work_keys_str_mv | AT zacharyjtickner riboswitchesforcontrolledexpressionoftherapeutictransgenesdeliveredbyadenoassociatedviralvectors AT michaelfarzan riboswitchesforcontrolledexpressionoftherapeutictransgenesdeliveredbyadenoassociatedviralvectors |