UMMS Affiliation

Horae Gene Therapy Center; Li Weibo Institute for Rare Diseases Research; Department of Microbiology and Physiological Systems; Viral Vector Core; Department of Neurosurgery; Department of Pediatrics; Department of Medicine

Publication Date


Document Type



Genetics and Genomics | Immunoprophylaxis and Therapy | Molecular Biology | Therapeutics


Pre-existing neutralizing antibody (NAb) against adeno-associated virus (AAV) commonly found in primates is a major host barrier that can severely compromise in vivo gene transfer by AAV vectors. To achieve proof-of-concept success in clinical development of recombinant AAV (rAAV)-based in vivo gene therapy, it is crucial to consider the potential interference of NAb and to enroll serologically compatible study subjects. In this study, we report a large AAV NAb dataset comprising multiple large animal species and AAV serotypes and compare two NAb assays based on in vitro or in vivo transduction inhibition, respectively. Together with previously published AAV seroepidemiology studies, these data can serve as a reference for selecting suitable serotypes, study subjects of large animal species, and potentially human patients for rAAV treatment. In addition, we modeled the intrathalamus rAAV9 delivery in the presence of circulating anti-AAV9 NAb generated by either pre-immunization or passive transfer of NAb-positive large animal serum to mice. The data showed that circulating NAb may not be the sole determinant to inhibit braintransduction. Other aspects of pre-existing AAV immunity following natural infection or rAAV administration may be further studied to establish a more accurate inclusion criterion for clinical studies employing intraparenchymal rAAV9 injections.


CNS gene transfer, adeno-associated virus, gene therapy, large animals, neutralizing antibody

Rights and Permissions

Copyright © 2018 The Authors. This is an open access article under the CC BY-NC-ND license (

DOI of Published Version



Mol Ther Methods Clin Dev. 2018 Oct 4;11:65-72. doi: 10.1016/j.omtm.2018.09.003. eCollection 2018 Dec 14. Link to article on publisher's site

Journal/Book/Conference Title

Molecular Therapy. Methods and Clinical Development

Related Resources

Link to article in PubMed

PubMed ID


Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.



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