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.
2024
Fast, accurate ranking of engineered proteins by target binding propensity using structure modeling
April 6 2024, Molecular Therapy
Ding X+, Chen X, Sullivan EE, Shay TF, Gradinaru V+
Synthetic dosage-compensating miRNA circuits allow precision gene therapy for Rett syndrome
March 14 2024, bioRxiv
Flynn MJ*, Mayfield AMH*, Du R, Gradinaru V+, Elowitz MB+
Human cell surface-AAV interactomes identify LRP6 as a blood-brain-barrier transcytosis receptor and immune cytokine IL3 as AAV9 binder
January 5 2024, bioRxiv
Shay TF*+, Jang S*, Chen X*, Walker B, Tebbutt C, Wolfe DA, Brittain TJ, Arokiaraj CM, Sullivan EE, Ding X, Wang T-Y, Lei Y, Chuapoco MR, Chou T-F, Gradinaru V+
2023
Spatial genomics of AAVs reveals mechanism of transcriptional crosstalk that enables targeted delivery of large genetic cargo
December 24 2023, bioRxiv
Coughlin GM*, Borsos M*, Appling N†, Barcelona BH†, Mayfield AMH, Mackey ED, Eser RA, Chen X, Ravindra Kumar S, Gradinaru V
Removal of a partial genomic duplication restores synaptic transmission and behavior in the MyosinVA mutant mouse Flailer
November 14 2023, BMC Biology
Bustos FJ, Pandian S, Haensgen H, Zhao J-P, Strouf H, Heidenreich M, Swiech L, Deverman BE, Gradinaru V, Zhang F, Constantine-Paton M
Characterization and quantification of adeno-associated virus capsid-loading states by multi-wavelength analytical ultracentrifugation with UltraScan
October 25 2023, Nanomedicine
Henrickson A, Ding X, Seal AG, Qu Z, Tomlinson L, Forsey J, Gradinaru V, Oka K, Demeler B
Adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain
July 10 2023, Nature Nanotechnology
Chuapoco MR*, Flytzanis NC*, Goeden N*, Octeau JC, Roxas KM, Chan KY, Scherrer J, Winchester J, Blackburn RJ, Campos LJ, Man KNM, Sun J, Chen X, Lefevre A, Singh VP, Arokiaraj CM, Shay TF, Vendemiatti J, Jang MJ, Mich JK, Bishaw Y, Gore BB, Omstead V, Taskin N, Weed N, Levi BP, Ting JT, Miller CT, Deverman BE, Pickel J, Tian L, Fox AS, Gradinaru V
Functional gene delivery to and across brain vasculature of systemic AAVs with endothelial-specific tropism in rodents and broad tropism in primates
June 8 2023, Nature Communications
Chen X, Wolfe DA, Bindu DS, Zhang M, Taskin N, Goertsen D, Shay TF, Sullivan EE, Huang S-F, Ravindra Kumar S, Arokiaraj CM, Plattner VM, Campos LJ, Mich JK, Monet D, Ngo V, Ding X, Omstead V, Weed N, Bishaw Y, Gore BB, Lein ES, Akrami A, Miller C, Levi BP, Keller A, Ting JT, Fox AS, Eroglu C, Gradinaru V
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
2022
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
2021
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
2020
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
2019
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
2018
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
2017
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
2016
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