John Chiorini, Ph.D.
NIH/NIDCR
Building 10, Room 1N113
10 Center Dr. MSC 1190
Bethesda, MD 20892-1190
United States
Adeno-associated virus (AAV) vectors have several characteristics that make them attractive agents for gene therapy, including stability, ease of manipulation, low immunogenicity, and the ability to direct long term expression of transgenes. The overall research goal of Dr. Chiorini’s AAV Biology Section is to define the interactions of AAV with its target cell. By understanding these interactions and the biology of the virus, vectors with enhanced activity can be developed and existing vectors can be more finely targeted to specific applications.
Ongoing projects are looking at possibilities to use these vectors to treat diseases with unmet clinical need. Of special interest, are vectors that can target diseases of the salivary gland including radiation induced xerostomia and Sjögren's disease. In addition to developing gene therapy vectors targeted to the salivary gland, research projects investigate the etiology and epigenetic regulation of salivary gland dysfunction.
Biographical Sketch
Dr. John (Jay) Chiorini received a B.A. in biochemistry and molecular biology from the University of California, Santa Cruz, and a Ph.D. in genetics from George Washington University. Dr. Chiorini completed post-doctoral training fellowships at both the National Institutes of General Medical Science (NIGMS) in the pharmacology research and training program, and at the National Heart, Lung, and Blood Institute (NHLBI) at NIH. As a postdoctoral fellow, Dr. Chiorini’s research focused on the role of the Rep proteins in AAV replication and the virus lifecycle. He cloned some of the first non-AAV2 serotypes including AAV4 and AAV5. Dr. Chiorini joined the NIDCR in 1999 and currently serves as chief of the Adeno-Associated Virus Biology Section. Findings from the group’s research are in clinical development and early stage clinical trials at the NIH and around the world.
- Crispino G, Galindo Ramirez F, Campioni M, Zorzi V, Praetorius M, Di Pasquale G, Chiorini JA, Mammano F. In vivo genetic manipulation of inner ear connexin expression by bovine adeno-associated viral vectors. Sci Rep. 2017 Aug 4;7(1):6567.
- Corden A, Handelman B, Yin H, Cotrim A, Alevizos I, Chiorini JA. Neutralizing antibodies against adeno-associated viruses in Sjögren's patients: implications for gene therapy. Gene Ther. 2017 Apr;24(4):241-244.
- Weller ML, Gardener MR, Bogus ZC, Smith MA, Astorri E, Michael DG, Michael DA, Zheng C, Burbelo PD, Lai Z, Wilson PA, Swaim W, Handelman B, Afione SA, Bombardieri M, Chiorini JA. Hepatitis Delta Virus Detected in Salivary Glands of Sjögren's Syndrome Patients and Recapitulates a Sjögren's Syndrome-Like Phenotype in Vivo. Pathog Immun. 2016 May;1(1):12-40.
- Lai Z, Yin H, Cabrera-Pérez J, Guimaro MC, Afione S, Michael DG, Glenton P, Patel A, Swaim WD, Zheng C, Nguyen CQ, Nyberg F, Chiorini JA. Aquaporin gene therapy corrects Sjögren's syndrome phenotype in mice. Proc Natl Acad Sci U S A. 2016 May 17;113(20):5694-9.
- Gan L, O'Hanlon TP, Lai Z, Fannin R, Weller ML, Rider LG, Chiorini JA, Miller FW. Gene Expression Profiles from Disease Discordant Twins Suggest Shared Antiviral Pathways and Viral Exposures among Multiple Systemic Autoimmune Diseases. PLoS One. 2015 Nov 10;10(11):e0142486.
- Tseng YS, Gurda BL, Chipman P, McKenna R, Afione S, Chiorini JA, Muzyczka N, Olson NH, Baker TS, Kleinschmidt J, Agbandje-McKenna M. Adeno-associated virus serotype 1 (AAV1)- and AAV5-antibody complex structures reveal evolutionary commonalities in parvovirus antigenic reactivity. J Virol. 2015 Feb;89(3):1794-808.
- Afione S, DiMattia MA, Halder S, Di Pasquale G, Agbandje-McKenna M, Chiorini JA. Identification and mutagenesis of the adeno-associated virus 5 sialic acid binding region. J Virol. 2015 Feb;89(3):1660-72.
- Momot D, Zheng C, Yin H, Elbekai RH, Vallant M, Chiorini JA. Toxicity and biodistribution of the serotype 2 recombinant adeno-associated viral vector, encoding Aquaporin-1, after retroductal delivery to a single mouse parotid gland. PLoS One. 2014 Mar 25;9(3):e92832.
- Sallach J, Di Pasquale G, Larcher F, Niehoff N, Rübsam M, Huber A, Chiorini J, Almarza D, Eming SA, Ulus H, Nishimura S, Hacker UT, Hallek M, Niessen CM, Büning H. Tropism-modified AAV vectors overcome barriers to successful cutaneous therapy. Mol Ther. 2014 May;22(5):929-39.