Gene Delivery

We are developing custom recombinant adeno-associated viruses (AAVs) for more efficient and targeted gene transfer in vivo.

Gradinaru lab publications in PubMed and bioRxiv.


Primate-conserved carbonic anhydrase IV and murine-restricted LY6C1 enable blood-brain barrier crossing by engineered viral vectors

April 19 2023, Science Advances

Shay TF*+, Sullivan EE*, Ding X*, Chen X, Ravindra Kumar S, Goertsen D, Brown D, Crosby A, Vielmetter J, Borsos M, Wolfe DA, Lam AW, Gradinaru V+

Spatial transcriptomics for profiling the tropism of viral vectors in tissues

January 26 2023, Nature Biotechnology

Jang MJ, Coughlin GM, Jackson CR, Chen X, Chuapoco M, Vendemiatti JL, Wang AZ, Gradinaru V

Fast, accurate ranking of engineered proteins by receptor binding propensity using structural modeling

January 14 2023, bioRxiv

Ding X, Chen X, Sullivan EE, Shay TF, Gradinaru V

Functional gene delivery to and across brain vasculature of systemic AAVs with endothelial-specific tropism in rodents and broad tropism in primates

January 13 2023, bioRxiv

Chen X, Wolfe DA, Bindu DS, Zhang M, Taskin N, Goertsen D, Shay TF, Sullivan E, Huang S-F, Kumar SR, Arokiaraj CM, Plattner V, Campos LJ, Mich J, Monet D, Ngo V, Ding X, Omstead V, Weed N, Bishaw Y, Gore B, Lein ES, Akrami A, Miller C, Levi BP, Keller A, Ting JT, Fox AS, Eroglu C, Gradinaru V

Primate-conserved Carbonic Anydrase IV and murine-restricted Ly6c1 are new targets for crossing the blood-brain barrier

January 13 2023, bioRxiv

Shay TF, Sullivan EE, Ding X, Chen X, Kumar SR, Goertsen D, Brown D, Vielmetter J, Borsos M, Lam AW, Gradinaru V


Targeting the lung epithelium after intravenous delivery by directed evolution of underexplored sites on the AAV capsid

August 9, 2022, Molecular Therapy–Methods & Clinical Development

Goertsen D, Goeden N, Flytzanis NC, Gradinaru V

Structural basis of receptor usage by the engineered capsid AAV-PHP.eB

August 9, 2022, Molecular Therapy–Methods & Clinical Development

Jang S, Shen HK, Ding X, Miles TF, Gradinaru V

Multimodal imaging of capsid and cargo reveals differential brain targeting and liver detargeting of systemically-administered AAVs

August 6, 2022, Biomaterials

Seo JW, Ajenjo J, Wu B, Robinson E, Raie MN, Wang J, Tumbale SK, Buccino P, Anders DA, Shen B, Habte FG, Beinat C, James ML, Reyes ST, Ravindra Kumar S, Miles TF, Lee JT, Gradinaru V, Ferrara KW

Engineered AAVs for non-invasive gene delivery to rodent and non-human primate nervous systems

May 27, 2022, Neuron

Chen X*, Ravindra Kumar S*, Adams CD, Yang D, Wang T, Wolfe DA, Arokiaraj CM, Ngo V, Campos LJ, Griffiths JA, Ichiki T, Mazmanian SK, Osborne PB, Keast JR, Miller CT, Fox AS, Chiu IM, Gradinaru VJ, Deverman BE, Pickel J, Fox AS, Gradinaru V

Intravenous gene transfer throughout the brain of infant Old World primates using AAV

Jan 11, 2022, bioRxiv

Chuapoco MR, Flytzanis N, Goeden N, Octeau JC, Roxas KM, Chan KY, Scherrer J, Winchester J, Blackburn RJ, Campos LJ, Arokiaraj CM, Miles TF, Jang MJ, Vendemiatti J, Deverman BE, Pickel J, Fox AS, Gradinaru V


AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset

Dec 9, 2021, Nature Neuroscience

Goertsen D, Flytzanis NC, Goeden N, Chuapoco MR, Cummins A, Chen Y, Fan Y, Zhang Q, Sharma J, Duan Y, Wang L, Feng G, Chen Y, Ip NY, Pickel J, Gradinaru V.

Deep Parallel Characterization of AAV Tropism and AAV-Mediated Transcriptional Changes via Single-Cell RNA Sequencing

Oct 12, 2021, Front. Immunol.

Brown D, Altermatt M, Dobreva T, Chen S, Wang A, Thomson M,  Gradinaru V.

Improved systemic AAV gene therapy with a neurotrophic capsid in Niemann-Pick disease type C1 mice

Aug 18, 2021, Life Sci Alliance 

Davidson CD, Gibson AL, Gu T, Baxter LL, Deverman BE, Beadle K, Incao AA, Rodriguez-Gil JL, Fujiwara H, Jiang X, Chandler RJ, Ory DS, Gradinaru V, Venditti CP, Pavan WJ

Brain-wide Cas9-mediated cleavage of a gene causing familial Alzheimer’s disease alleviates amyloid-related pathologies in mice

July 26, 2021, Nat Biomed Eng. 

Duan Y, Ye T, Qu Z, Chen Y, Miranda A, Zhou X, Lok KC, Chen Y, Fu AKY, Gradinaru V, Ip NY

Specific and behaviorally consequential astrocyte Gq GPCR signaling attenuation in vivo with iβARK

June 16, 2021, Neuron 

Jun Nagai, Arash Bellafard, Zhe Qu, Xinzhu Yu, Matthias Ollivier, Mohitkumar R Gangwani, Blanca Diaz-Castro, Giovanni Coppola, Sarah M Schumacher, Peyman Golshani, Viviana Gradinaru, Baljit S Khakh

Use of high-content imaging to quantify transduction of AAV-PHP viruses in the brain following systemic delivery

May 17, 2021, Brain Communications

Edward J Smith, Pamela P Farshim, Rachel Flomen, Samuel T Jones, Sean J McAteer, Benjamin E Deverman, Viviana Gradinaru, Gillian P Bates 

Enhancer viruses for combinatorial cell-subclass-specific labeling

March 30, 2021, Neuron

Lucas T. Graybuck, Tanya L. Daigle, Adriana E. Sedeño-Cortés, Miranda Walker, Brian Kalmbach, Garreck H. Lenz, Elyse Morin, Thuc Nghi Nguyen, Emma Garren, Jacqueline L. Bendrick, Tae Kyung Kim, Thomas Zhou, Marty Mortrud, Shenqin Yao, La’ Akea Siverts, Rachael Larsen, Bryan B. Gore, Eric R. Szelenyi, Cameron Trader, Pooja Balaram, Cindy T.J. van Velthoven, Megan Chiang, John K. Mich, Nick Dee, Jeff Goldy, Ali H. Cetin, Kimberly Smith, Sharon W. Way, Luke Esposito, Zizhen Yao, Viviana Gradinaru, Susan M. Sunkin, Ed Lein, Boaz P. Levi, Jonathan T. Ting, Hongkui Zeng, Bosiljka Tasic 

Functional enhancer elements drive subclass-selective expression from mouse to primate neocortex

March 30, 2021, Cell Reports

John K Mich, Lucas T Graybuck, Erik E Hess, Joseph T Mahoney, Yoshiko Kojima, Yi Ding, Saroja Somasundaram, Jeremy A Miller, Brian E Kalmbach, Cristina Radaelli, Bryan B Gore, Natalie Weed, Victoria Omstead, Yemeserach Bishaw, Nadiya V Shapovalova, Refugio A Martinez, Olivia Fong, Shenqin Yao, Marty Mortrud, Peter Chong, Luke Loftus, Darren Bertagnolli, Jeff Goldy, Tamara Casper, Nick Dee, Ximena Opitz-Araya, Ali Cetin, Kimberly A Smith, Ryder P Gwinn, Charles Cobbs, Andrew L Ko, Jeffrey G Ojemann, C Dirk Keene, Daniel L Silbergeld, Susan M Sunkin, Viviana Gradinaru, Gregory D Horwitz, Hongkui Zeng, Bosiljka Tasic, Ed S Lein, Jonathan T Ting, Boaz P Levi 


Broad gene expression throughout the mouse and marmoset brain after intravenous delivery of engineered AAV capsids

June 17, 2020, BioRxiv

Nicholas C. Flytzanis, Nick Goeden, David Goertsen, Alexander Cummins, James Pickel, Viviana Gradinaru

Positron emission tomography imaging of novel AAV capsids maps rapid brain accumulation

April 30, 2020, Nature Communications

Jai Woong Seo, Elizabeth S. Ingham, Lisa Mahakian, Spencer Tumbale, Bo Wu, Sadaf Aghevlian, Shahin Shams, Mo Baikoghli, Poorva Jain, Xiaozhe Ding, Nick Goeden, Tatyana Dobreva, Nicholas C. Flytzanis, Michael Chavez, Kratika Singhal, Ryan Leib, Michelle L. James, David J. Segal, R. Holland Cheng, Eduardo A. Silva, Viviana Gradinaru, Katherine W. Ferrara

Multiplexed Cre-dependent selection yields systemic AAVs for targeting distinct brain cell types

April 20, 2020, Nature Methods

Sripriya Ravindra Kumar, Timothy F. Miles, Xinhong Chen, David Brown, Tatyana Dobreva, Qin Huang, Xiaozhe Ding, Yicheng Luo, Pétur H. Einarsson, Alon Greenbaum, Min J. Jang, Benjamin E. Deverman, Viviana Gradinaru

LRP1 is a master regulator of tau uptake and spread

April 1, 2020, Nature

Jennifer N. Rauch, Gabriel Luna, Elmer Guzman, Morgane Audouard, Collin Challis, Youssef E. Sibih, Carolina Leshuk, Israel Hernandez, Susanne Wegmann, Bradley T. Hyman, Viviana Gradinaru, Martin Kampmann, Kenneth S. Kosik.

RecV recombinase system for in vivo targeted optogenomic modifications of single cells or cell populations

March 23, 2020, Nature Methods

Shenqin Yao, Peng Yuan, Ben Ouellette, Thomas Zhou, Marty Mortrud, Pooja Balaram, Soumya Chatterjee, Yun Wang, Tanya L. Daigle, Bosiljka Tasic, Xiuli Kuang, Hui Gong, Qingming Luo, Shaoqun Zeng, Andrew Curtright, Ajay Dhaka, Anat Kahan, Viviana Gradinaru, Radosław Chrapkiewicz, Mark Schnitzer, Hongkui Zeng, Ali Cetin

Gut-seeded α-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice

February 17, 2020, Nature Neuroscience

Collin Challis, Acacia Hori, Timothy R. Sampson, Bryan B. Yoo, Rosemary C. Challis, Adam M. Hamilton, Sarkis K. Mazmanian, Laura A. Volpicelli-Daley, Viviana Gradinaru


Machine learning-guided channelrhodopsin engineering enables minimally invasive optogenetics

October 14, 2019, Nature Methods

Claire N. Bedbrook, Kevin K. Yang, J. Elliott Robinson, Elisha D. Mackey, Viviana Gradinaru, Frances H. Arnold

Optical dopamine monitoring with dLight1 reveals mesolimbic phenotypes in a mouse model of neurofibromatosis type 1

September 23, 2019, eLife

J Elliott Robinson, Gerard M Coughlin, Acacia M Hori, Jounhong Ryan Cho, Elisha D Mackey, Zeynep Turan, Tommaso Patriarchi, Lin Tian, Viviana Gradinaru

Identification of peripheral neural circuits that regulate heart rate using optogenetic and viral vector strategies

April 26, 2019, Nature Communications

Pradeep S. Rajendran, Rosemary C. Challis, Charless C. Fowlkes, Peter Hanna, John D. Tompkins, Maria C. Jordan, Sarah Hiyari, Beth A. Gabris-Weber, Alon Greenbaum, Ken Y. Chan, Benjamin E. Deverman, Heike Münzberg, Jeffrey L. Ardell, Guy Salama, Viviana Gradinaru, Kalyanam Shivkumar

TRIM9-Mediated Resolution of Neuroinflammation Confers Neuroprotection upon Ischemic Stroke in Mice

April 9, 2019, Cell Reports

Jianxiong Zeng, Yaoming Wang, Zhifei Luo, Lin-Chun Chang, Ji Seung Yoo, Huan Yan, Younho Choi, Xiaochun Xie, Benjamin E. Deverman, Viviana Gradinaru, Stephanie L. Gupton, Berislav V. Zlokovic, Zhen Zhao, Jae U. Jung

Functional enhancer elements drive subclass-selective expression from mouse to primate neocortex

February 19, 2019,

John K. Mich, Lucas T. Graybuck, Erik E. Hess, Joseph T. Mahoney, Yoshiko Kojima, Yi Ding, Saroja Somasundaram, Jeremy A. Miller, Natalie Weed, Victoria Omstead, Yemeserach Bishaw, Nadiya V. Shapovalova, Refugio A. Martinez, Olivia Fong, Shenqin Yao, Marty Mortrud, Peter Chong, Luke Loftus, Darren Bertagnolli, Jeff Goldy, Tamara Casper, Nick Dee, Ximena Opitz-Araya, Ali Cetin, Kimberly A. Smith, Ryder P. Gwinn, Charles Cobbs, Andrew. L. Ko, Jeffrey G. Ojemann, C. Dirk Keene, Daniel. L. Silbergeld, Susan M. Sunkin, Viviana Gradinaru, Gregory D. Horwitz, Hongkui Zeng, Bosiljka Tasic, Ed S. Lein, Jonathan T. Ting, Boaz P. Levi

Systemic AAV vectors for widespread and targeted gene delivery in rodents

January 8, 2019, Nature Protocols

Rosemary C. Challis, Sripriya Ravindra Kumar, Ken Y. Chan, Collin Challis, Keith Beadle, Min J. Jang, Hyun Min Kim, Pradeep S. Rajendran, John D. Tompkins, Kalyanam Shivkumar, Benjamin E. Deverman, Viviana Gradinaru


Identification of peripheral neural circuits that regulate heart rate using optogenetic and viral vector strategies

October 29, 2018,

Pradeep S. Rajendran, Rosemary C. Challis, Charless C. Fowlkes, Peter Hanna, John D. Tompkins, Maria C. Jordan, Sarah Hiyari, Beth A. Gabris-Weber, Alon Greenbaum, Ken Y. Chan, Benjamin E. Deverman, Heike Münzberg, Jeffrey L. Ardell, Guy Salama, Viviana Gradinaru, Kalyanam Shivkumar

Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors

May 31, 2018, Science

Tommaso Patriarchi, Jounhong Ryan Cho, Katharina Merten, Mark W. Howe, Aaron Marley, Wei-Hong Xiong, Robert W. Folk, Gerard Joey Broussard, Ruqiang Liang, Min Jee Jang, Haining Zhong, Daniel Dombeck, Mark von Zastrow, Axel Nimmerjahn, Viviana Gradinaru, John T. Williams, Lin Tian

The Neuropeptide Tac2 Controls a Distributed Brain State Induced by Chronic Social Isolation Stress

May 17, 2018, Cell

Moriel Zelikowsky, May Hui, Tomomi Karigo, Andrea Choe, Bin Yang, Mario R. Blanco, Keith Beadle, Viviana Gradinaru, Benjamin E. Deverman, David J. Anderson

Viral Strategies for Targeting the Central and Peripheral Nervous Systems

April 30, 2018, Annual Review of Neuroscience

Claire N. Bedbrook, Benjamin E. Deverman, Viviana Gradinaru


Overriding sleep

October 26, 2017, Science

Viviana Gradinaru

Dopaminergic dysfunction in neurodevelopmental disorders: recent advances and synergistic technologies to aid basic research

August 30, 2017, Current Opinion in Neurobiology

J Elliott Robinson, Viviana Gradinaru

Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems

June 26, 2017, Nature Neuroscience

Ken Y Chan, Min J Jang, Bryan B Yoo, Alon Greenbaum, Namita Ravi, Wei-Li Wu, Luis Sánchez-Guardado, Carlos Lois, Sarkis K Mazmanian, Benjamin E Deverman, Viviana Gradinaru

Global Representations of Goal-Directed Behavior in Distinct Cell Types of Mouse Neocortex

May 17, 2017, Neuron

William E. Allen, Isaac V. Kauvar, Michael Z. Chen, Ethan B. Richman, Samuel J. Yang, Ken Chan, Viviana Gradinaru, Benjamin E. Deverman, Liqun Luo, Karl Deisseroth


Extracting structural and functional features of widely distributed biological circuits with single cell resolution via tissue clearing and delivery vectors

July 6, 2016, Current Opinion in Biotechnology

Jennifer Brooke Treweek, Viviana Gradinaru

Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain

February 1, 2016, Nature Biotechnology

Benjamin E Deverman, Piers L Pravdo, Bryan P Simpson, Sripriya Ravindra Kumar, Ken Y Chan, Abhik Banerjee, Wei-Li Wu, Bin Yang, Nina Huber, Sergiu P Pasca, Viviana Gradinaru