Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain

By Benjamin E. Deverman, Piers L. Pravdo, Bryan P. Simpson, Sripriya Ravindra Kumar, Ken Y. Chan, Abhik K. Banerjee, Wei-Li Wu, Bin Yang, Nina Huber, S. Pașca and 1 more. Nature Biotechnology, 2016

944 citations recorded by the source corpus.

Recombinant adeno-associated viruses (rAAVs) are commonly used vehicles for in vivo gene transfer. However, the tropism repertoire of naturally occurring AAVs is limited, prompting a search for novel AAV capsids with desired characteristics. Here we describe a capsid selection method, called Cre recombination–based AAV targeted evolution (CREATE), that enables the development of AAV capsids that more efficiently transduce defined Cre-expressing cell populations in vivo. We use CREATE to generate AAV variants that efficiently and widely transduce the adult mouse central nervous system (CNS) after intravenous injection. One variant, AAV-PHP.B, transfers genes throughout the CNS with an efficiency that is at least 40-fold greater than that of the current standard, AAV9 (refs. 14,15,16,17), and transduces the majority of astrocytes and neurons across multiple CNS regions. In vitro, it transduces human neurons and astrocytes more efficiently than does AAV9, demonstrating the potential of CREATE to produce customized AAV vectors for biomedical applications.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/b8bb20b712d6bbe332306970896e4db8b657c69e

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In Genetics

1. Guangping Gao
2. Wei Zhan
3. Thomas L. Gallagher
4. Jiang-Hui Wang
5. Dominic J. Gessler
6. F. Mingozzi

In Molecular Biology

1. Guangping Gao
2. Wei Zhan
3. Thomas L. Gallagher
4. Jiang-Hui Wang
5. Dominic J. Gessler
6. F. Mingozzi

Citations in the corpus

• Adeno-associated virus as a delivery vector for gene therapy of human diseases (2024, background): “86 CREATE was used to generate AAV-PHP.”
• Emerging Issues in AAV-Mediated In Vivo Gene Therapy (2017, background): “High-throughput approaches employing libraries of randomly modified capsids followed by in vivo selection also lead to the identification of powerful “synthetic”AAV vectors.(21) One of the limitations of testing the liver transduction ability of AAV vectors in mouse (and other small-animal models) i”