University of California, Berkeley

Welcome to the Flannery Lab

We focus on advancing preclinical gene therapies for inherited retinal degenerative diseases through the development and optimization of adeno-associated viral (AAV) vectors for targeted gene delivery and vision restoration.

Our Research Our Team Publications

01

Retinal Degeneration

Over 100,000 Americans of all ages suffer from inherited retinal diseases, which cause a progressive loss of vision. In most IRDs, disease begins in the rods, causing vision loss from the periphery to the center, leaving patients unable to navigate their surroundings. Retinal degeneration and blindness result from the loss of rod and cone photoreceptors due to mutations in these cells or in their closely interacting and supportive retinal pigment epithelium, from environmental or poorly defined age-related factors, or the actions of other retinal neurons, glia or vascular elements. Relatively little is known about why precisely why photoreceptors die in any of the many retinal degenerations, and very little effective therapy exists for most of these diseases. One of the major goals of our laboratory is to develop therapeutic approaches that will restore vision in retinal degenerations.

Motivation

02

AAV Gene Therapy

Gene therapy has vast potential for treating and potentially curing a number of retinal diseases, including inherited retinal degenerative diseases, glaucoma, and age-related macular degeneration. However, gene delivery technologies require significant improvements in cellular targeting, efficiency, and safety before promising findings in animal studies are translated to the clinic. The lab uses mouse models of inherited retinal degenerations to optimize transduction and gene delivery of specific retinal cell types.

Mechanism

03

Optogenetic Restoration

Can the inner retina be manipulated in a way to add a light-receptive function, and thereby serve to transduce light in retinas that have lost their photoreceptors due to various retinal degenerations? In collaboration, we use microbial channelrhodopsins to target the surviving inner retina, restoring vision in mouse models of inherited retinal degenerations. This compensates for their loss of input from photoreceptors, restoring light responsiveness to the retina and sending information to the brain to restore vision. This approach is independent of the mutations that result in photoreceptor degeneration. Exceptions to this approach may be diseases that cause RPE cell death, such as choroideremia. We employ sophisticated behavioral analysis to test not only the restoration of the ability to tell light from dark or flashing from steady light, but the overall visual quality of the animal. Success of this program represents a major step in the development of optogenetic therapies.

Methodology

The Team

Minds behind the science

John Flannery

John Flannery

Principal Investigator

Professor of Vision Science and Neuroscience Division of Molecular and Cell Biology. Faculty member of the Helen Wills Neuroscience Institute and School of Optometry. Prof. Flannery has spent decades pioneering gene therapy approaches for inherited retinal degenerations, with contributions spanning AAV vector engineering, optogenetic vision restoration, and translational therapies now approaching clinical application.

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Lab Management

Meike Visel

Meike Visel

Lab Manager
AAV Packaging Specialist
Since 2005

Medical Laboratory Science, Germany

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Graduate Students

Beatrice Le

Beatrice Le

Vision Science PhD
Since Aug 2023

Optogenetic gene therapies in murine models · co-mentored with Dr. Rowland Taylor

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Sonali Singh

Sonali Singh

Vision Science PhD
Since Aug 2021

Novel AAV gene therapy for dry AMD and LCA2

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Lobna Hamed

Lobna Hamed

Vision Science PhD
Since Aug 2024

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Poorna Sharma

Poorna Sharma

Vision Science PhD
Since Aug 2024

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Undergraduate Researchers

Daniel Kang

Daniel Kang

Chemical Biology · Data Science
Class of 2026

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Tyler Houston

Tyler Houston

Chemical Biology
Class of 2026

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Beth Wade

Beth Wade

Molecular & Cell Biology
Class of 2026

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Vivian Mai Huong Tran

Vivian M.H. Tran

Data Science
Class of 2027

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Basma Levar Jeqa

Basma Levar Jeqa

Molecular & Cell Biology
Class of 2027

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Evan Kwong

Evan Kwong

Molecular & Cell Biology
Class of 2028

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Honorable Mention

Scott Geller

Scott Geller

Former Postdoc
Director, UC Berkeley Sequencing Facility

Always has an open ear and good advice on all science-related questions.

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Lab Life & Updates

News & Moments

January 15, 2026

Congratulations to Lobna for passing her Qualifying Exam!

May 2025

Congratulations to Sabrina, Adithya and Aneal on graduating! We will miss you and wish you all the best for the future.

February 21, 2025

Congratulations to Beatrice for passing her Qualifying Exam!

Lab Life Gallery

Group Picture Halloween 2025

Group Picture — Halloween 2025

Group Picture Spring 2024

Group Picture — Spring 2024

Group Meeting 2020

Group Meeting — 2020

Group Picture 2014

Group Picture — 2014

Group Picture 2007

Group Picture — 2007

Graduate Students October 2025

Graduate Students — October 2025

Goodbye Meet-up 2025

Goodbye Meet-up — 2025 Graduates

Birthday Lunch at Jupiter 2024

Birthday Lunch at Jupiter — 2024

Halloween 2024

Halloween Group Picture — 2024

Victory Point Cafe 2024

Birthday Lunch at Victory Point Cafe — 2024

Jupiter Lab Lunch Summer 2023

Jupiter Lab Lunch — Summer 2023

Birthday Lunch 2022

Birthday Lunch — 2022

Graduation Cecile Fortuny

Graduation — Cecile Fortuny

Escape Room 2016

Escape Room Outing — 2016

Graduation 2006

Graduation — 2006

Discoveries

Selected Publications

2025

Optogenetic restoration of high-sensitivity vision using ChRmine- and ChroME-based channelrhodopsins

Fong VC, Le BM, Stefanov A, Lee V, Park S, Sivakumar A, Spatny S, Visel M, Taylor WR, Brohawn SG, Flannery JG.

Sci Rep. 2025 Jul 1;15(1):21204.

2023

A Systematic Review of Optogenetic Vision Restoration: History, Challenges, and New Inventions from Bench to Bedside

Stefanov A, Flannery JG.

Cold Spring Harbor Perspectives in Medicine. 2023;13(6):a041304.

2022

Photopharmacology for vision restoration

Berry MH, Holt A, Broichhagen J, Donthamsetti P, Flannery JG, Isacoff EY.

Current Opinion in Pharmacology. 2022;65:102259.

2022

Targeting ON-bipolar cells by AAV gene therapy stably reverses LRIT3-congenital stationary night blindness

Miyadera K, Santana E, Roszak K, Iffrig S, Visel M, Iwabe S, Boyd RF, Bartoe JT, Sato Y, Gray A, Ripolles-Garcia A, Dufour VL, Byrne LC, Flannery JG, Beltran WA, Aguirre GD.

Proceedings of the National Academy of Sciences of the United States of America. 2022;119(13):e2117038119.

2021

scAAVengr, a transcriptome-based pipeline for quantitative ranking of engineered AAVs with single-cell resolution

Öztürk BE, Johnson ME, Kleyman M, Turunç S, He J, Jabalameli S, Xi Z, Visel M, Dufour VL, Iwabe S, Pompeo Marinho LFL, Aguirre GD, Sahel JA, Schaffer DV, Pfenning AR, Flannery JG, Beltran WA, Stauffer WR, Byrne LC.

eLife. 2021;10:e64175.

2021

Outcomes of progranulin gene therapy in the retina are dependent on time and route of delivery

Zin EA, Han D, Tran J, Morisson-Welch N, Visel M, Kuronen M, Flannery JG.

Molecular Therapy. Methods & Clinical Development. 2021;22:40-51.

2021

AAV Induced Expression of Human Rod and Cone Opsin in Bipolar Cells of a Mouse Model of Retinal Degeneration

McClements ME, Staurenghi F, Visel M, Flannery JG, MacLaren RE, Cehajic-Kapetanovic J.

BioMed Research International. 2021;1-8.

2020

In vivo directed evolution of AAV in the primate retina

Byrne LC, Day TP, Visel M, Strazzeri JA, Fortuny C, Dalkara D, Merigan WH, Schaffer D, Flannery JG.

JCI Insight. 2020 May 21;5(10):e135112.

2019

Restoration of high-sensitivity and adapting vision with a cone opsin

Berry MH, Holt A, Salari A, Veit J, Visel M, Levitz J, Aghi K, Gaub BM, Siyver B, Flannery JG, Isacoff EY.

Nature Communications. 2019;10(1):1221. Published 2019 Mar 15.

2018

Innovative Optogenetic Strategies for Vision Restoration

Baker CK, Flannery JG.

Frontiers in Cellular Neuroscience. 2018;12:316. Published 2018 Sep 21.

2018

Mutation-Independent Gene Therapies for Rod-Cone Dystrophies

Fortuny C, Flannery JG.

Advances in Experimental Medicine and Biology. 2018.

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2018

Screening for Neutralizing Antibodies Against Natural and Engineered AAV Capsids in Nonhuman Primate Retinas

Day TP, Byrne LC, Flannery JG, Schaffer DV.

Methods in Molecular Biology. 2018;1715:239-249.

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2018

Optogenetic Retinal Gene Therapy with the Light Gated GPCR Vertebrate Rhodopsin

Gaub BM, Berry MH, Visel M, Holt A, Isacoff EY, Flannery JG.

Methods in Molecular Biology. 2018;1715:177-189.

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2015

Neuron-glia signaling in developing retina mediated by neurotransmitter spillover

Rosa JM, Bos R, Sack GS, et al.

eLife. 2015;4:e09590.

2015

Optogenetic Vision Restoration Using Rhodopsin for Enhanced Sensitivity

Gaub BM, Berry MH, Holt AE, Isacoff EY, Flannery JG.

Molecular Therapy. 2015;23(10):1562-1571.

2015

The expression pattern of systemically injected AAV9 in the developing mouse retina is determined by age

Byrne LC, Lin YJ, Lee T, Schaffer DV, Flannery JG.

Molecular Therapy. 2015 Feb;23(2):290-6. Epub 2014 Sep 16.

2015

Viral-mediated RdCVF and RdCVFL expression protects cone and rod photoreceptors in retinal degeneration

Byrne LC, Dalkara D, Luna G, Fisher SK, Clérin E, Sahel JA, Léveillard T, Flannery JG.

Journal of Clinical Investigation. 2015 Jan;125(1):105-16. Epub 2014 Nov 21.

2014

Retinoschisin gene therapy in photoreceptors, Müller glia or all retinal cells in the Rs1h-/- mouse

Byrne LC, Oztürk BE, Lee T, Fortuny C, Visel M, Dalkara D, Schaffer DV, Flannery JG.

Gene Therapy. 2014 Apr 3.

2014

Advances in AAV Vector Development for Gene Therapy in the Retina

Day TP, Byrne LC, Schaffer DV, Flannery JG.

Advances in Experimental Medicine and Biology. 2014;801:687-93.

2013

In vivo-directed evolution of a new adeno-associated virus for therapeutic outer retinal gene delivery from the vitreous

Dalkara D, Byrne LC, Klimczak RR, Visel M, Yin L, Merigan WH, Flannery JG, Schaffer DV.

Science Translational Medicine. 2013 Jun 12;5(189):189ra76.

2013

Adeno-associated viral vectors for gene therapy of inherited retinal degenerations

Flannery JG, Visel M.

Methods in Molecular Biology. 2013;935:351-69.

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2013

AAV-mediated, optogenetic ablation of Müller Glia leads to structural and functional changes in the mouse retina

Byrne LC, Khalid F, Lee T, Zin EA, Greenberg KP, Visel M, Schaffer DV, Flannery JG.

PLoS One. 2013 Sep 27;8(9):e76075.

2012

Enhanced gene delivery to the neonatal retina through systemic administration of tyrosine-mutated AAV9

Dalkara D, Byrne LC, Lee T, Hoffmann NV, Schaffer DV, Flannery JG.

Gene Therapy. 2012 Feb;19(2):176-81.

2011

AAV mediated GDNF secretion from retinal glia slows down retinal degeneration in a rat model of retinitis pigmentosa

Dalkara D, Kolstad KD, Guerin KI, Hoffmann NV, Visel M, Klimczak RR, Schaffer DV, Flannery JG.

Molecular Therapy. 2011 Sep;19(9):1602-8.

2011

LiGluR restores visual responses in rodent models of inherited blindness

Caporale N, Kolstad KD, Lee T, Tochitsky I, Dalkara D, Trauner D, Kramer R, Dan Y, Isacoff EY, Flannery JG.

Molecular Therapy. 2011 Jul;19(7):1212-9.

2010

Changes in adeno-associated virus-mediated gene delivery in retinal degeneration

Kolstad KD, Dalkara D, Guerin K, Visel M, Hoffmann N, Schaffer DV, Flannery JG.

Human Gene Therapy. 2010 May;21(5):571-8.

2009

Inner limiting membrane barriers to AAV-mediated retinal transduction from the vitreous

Dalkara D, Kolstad KD, Caporale N, Visel M, Klimczak RR, Schaffer DV, Flannery JG.

Molecular Therapy. 2009 Dec;17(12):2096-102.

2009

Molecular evolution of adeno-associated virus for enhanced glial gene delivery

Koerber JT, Klimczak R, Jang JH, Dalkara D, Flannery JG, Schaffer DV.

Molecular Therapy. 2009 Dec;17(12):2088-95.

2009

A novel adeno-associated viral variant for efficient and selective intravitreal transduction of rat Müller cells

Klimczak RR, Koerber JT, Dalkara D, Flannery JG, Schaffer DV.

PLoS One. 2009 Oct 14;4(10):e7467.

2009

CLRN1 is nonessential in the mouse retina but is required for cochlear hair cell development

Geller SF, Guerin KI, Visel M, Pham A, Lee ES, Dror AA, Avraham KB, Hayashi T, Ray CA, Reh TA, Bermingham-McDonogh O, Triffo WJ, Bao S, Isosomppi J, Västinsalo H, Sankila EM, Flannery JG.

PLoS Genetics. 2009 Aug;5(8):e1000607.

2008

Systemic aminoglycoside treatment in rodent models of retinitis pigmentosa

Guerin K, Gregory-Evans CY, Hodges MD, Moosajee M, Mackay DS, Gregory-Evans K, Flannery JG.

Experimental Eye Research. 2008 Sep;87(3):197-207.

2008

In vitro analysis of promoter activity in Müller cells

Geller SF, Ge PS, Visel M, Flannery JG.

Molecular Vision. 2008 Apr 23;14:691-705.

2007

Transport of truncated rhodopsin and its effects on rod function and degeneration

Lee ES, Flannery JG.

Investigative Ophthalmology & Visual Science. 2007 Jun;48(6):2868-76.

2007

Functional promoter testing using a modified lentiviral transfer vector

Geller SF, Ge PS, Visel M, Greenberg KP, Flannery JG.

Molecular Vision. 2007 May 17;13:730-9.

2007

Targeted transgene expression in muller glia of normal and diseased retinas using lentiviral vectors

Greenberg KP, Geller SF, Schaffer DV, Flannery JG.

Investigative Ophthalmology & Visual Science. 2007 Apr;48(4):1844-52.

2006

Characterization of peripherin/rds and rom-1 transport in rod photoreceptors of transgenic and knockout animals

Lee ES, Burnside B, Flannery JG.

Investigative Ophthalmology & Visual Science. 2006 May;47(5):2150-60.

2006

Looking within for vision

Flannery JG, Greenberg KP.

Neuron. 2006 Apr 6;50(1):1-3. Erratum in: Neuron. 2006 Apr 20;50(2):341.

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2006

Gene delivery to the retina using lentiviral vectors

Greenberg KP, Lee ES, Schaffer DV, Flannery JG.

Advances in Experimental Medicine and Biology. 2006;572:255-66.

2001

Glial cell line derived neurotrophic factor delays photoreceptor degeneration in a transgenic rat model of retinitis pigmentosa

McGee Sanftner LH, Abel H, Hauswirth WW, Flannery JG.

Molecular Therapy. 2001 Dec;4(6):622-9.

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2001

Recombinant AAV-mediated delivery of a tet-inducible reporter gene to the rat retina

McGee Sanftner LH, Rendahl KG, Quiroz D, Coyne M, Ladner M, Manning WC, Flannery JG.

Molecular Therapy. 2001 May;3(5 Pt 1):688-96.

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2001

Two animal models of retinal degeneration are rescued by recombinant adeno-associated virus-mediated production of FGF-5 and FGF-18

Green ES, Rendahl KG, Zhou S, Ladner M, Coyne M, Srivastava R, Manning WC, Flannery JG.

Molecular Therapy. 2001 Apr;3(4):507-15.

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2000

Retinal degeneration is slowed in transgenic rats by AAV-mediated delivery of FGF-2

Lau D, McGee LH, Zhou S, Rendahl KG, Manning WC, Escobedo JA, Flannery JG.

Investigative Ophthalmology & Visual Science. 2000 Oct;41(11):3622-33.

2000

Characterization of rhodopsin mis-sorting and constitutive activation in a transgenic rat model of retinitis pigmentosa

Green ES, Menz MD, LaVail MM, Flannery JG.

Investigative Ophthalmology & Visual Science. 2000 May;41(6):1546-53.

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We are always looking for motivated collaborators passionate about restoring sight. If you are interested in exploring a scientific partnership, please reach out.

Location 120 Barker Hall, UC Berkeley, California 94720

Department Molecular and Cell Biology & Vision Science

Institute Helen Wills Neuroscience Institute

School School of Optometry, UC Berkeley

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