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PLoS One. 2018 Jun 29;13(6):e0200060. doi: 10.1371/journal.pone.0200060. eCollection 2018.

Development and testing of AAV-delivered single-chain variable fragments for the treatment of methamphetamine abuse.

Author information

1
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
2
Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
3
The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
4
The University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.

Abstract

Methamphetamine (METH) substance abuse disorders have major impact on society, yet no medications have proven successful at preventing METH relapse or cravings. Anti-METH monoclonal antibodies can reduce METH brain concentrations; however, this therapy has limitations, including the need for repeated dosing throughout the course of addiction recovery. An adeno-associated viral (AAV)-delivered DNA sequence for a single-chain variable fragment could offer long-term, continuous expression of anti-METH antibody fragments. For these studies, we injected mice via tail vein with 1 x 10(12) vector genomes of two AAV8 scFv constructs and measured long-term expression of the antibody fragments. Mice expressed each scFv for at least 212 days, achieving micromolar scFv concentrations in serum. In separate experiments 21 days and 50 days after injecting mice with AAV-scFvs mice were challenged with METH in vivo. The circulating scFvs were capable of decreasing brain METH concentrations by up to 60% and sequestering METH in serum for 2 to 3 hrs. These results suggest that AAV-delivered scFv could be a promising therapy to treat methamphetamine abuse.

PMID:
29958300
PMCID:
PMC6025879
DOI:
10.1371/journal.pone.0200060
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

SMO has financial interests in and serves as Chief Scientific Officer of InterveXion Therapeutics LLC (Little Rock, AR), a pharmaceutical biotechnology company focused on treating human drug addiction with antibody-based therapies. PM receives research funding from NovoNordisk A/S, through competitive grants from the “Bayer Hemophilia Awards Program” and salary (spouse) from Bristol-Myers Squibb. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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