# Rescuing AAV gene transfer from neutralizing antibodies with an IgG-degrading enzyme

Article · Elmore ZC, Oh DK, Simon KE, Fanous MM, Asokan A

- Archive id: doi:10.1172/jci.insight.139881
- Published: 2020-09-17
- Venue: JCI insight
- DOI: https://doi.org/10.1172/jci.insight.139881
- PMID: 32941184
- PMCID: PMC7566709
- Citations: 120
- Source URL: https://doi.org/10.1172/jci.insight.139881
- PDF: https://europepmc.org/articles/PMC7566709/pdf
- Provenance: europepmc

## Abstract

Preexisting humoral immunity to recombinant adeno-associated virus (AAV) vectors restricts the treatable patient population and efficacy of human gene therapies. Approaches to clear neutralizing antibodies (NAbs), such as plasmapheresis and immunosuppression, are either ineffective or cause undesirable side effects. Here, we describe a clinically relevant strategy to rapidly and transiently degrade NAbs before AAV administration using an IgG-degrading enzyme (IdeZ). We demonstrate that recombinant IdeZ efficiently cleaved IgG in dog, monkey, and human antisera. Prophylactically administered IdeZ cleaved circulating human IgG in mice and prevented AAV neutralization in vivo. In macaques, a single intravenous dose of IdeZ rescued AAV transduction by transiently reversing seropositivity. Importantly, IdeZ efficiently cleaved NAbs and rescued AAV transduction in mice passively immunized with individual human donor sera representing a diverse population. Our antibody clearance approach presents a potentially new paradigm for expanding the prospective patient cohort and improving efficacy of AAV gene therapy.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Gene & Cell Therapy](https://space-kitty.com/topics/gene-cell-therapy)

Cited in dossiers:
- [Gene & Cell Therapy: State of the Field (October 2026)](https://space-kitty.com/dossiers/gene-cell-therapy)

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