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Jacob S Brenner, MD, PhD
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Assistant Professor of Medicine (Pulmonary, Allergy and Critical Care)
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Attending Physician, Hospital of the University of Pennsylvania
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Co-Director, Penn's Center for Targeted Therapeutics & Translational Nanomedicine
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Department: Medicine
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Graduate Group Affiliations
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Contact information
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3450 Hamilton Walk
41 Stemmler Building, Office #220
Philadelphia, PA 19104
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41 Stemmler Building, Office #220
Philadelphia, PA 19104
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Office: 215-662-2222
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Publications
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Links
da Search PubMed for articles
79 Brenner Bioengineering Lab
6e Brenner Bioengineering Lab
66 LinkedIn account
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da Search PubMed for articles
79 Brenner Bioengineering Lab
6e Brenner Bioengineering Lab
66 LinkedIn account
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Education:
21 7 BA 1e (Molecular Biology) c
2d Princeton University, 2001.
21 8 PhD 40 (Chemical & Systems Biology / Molecular Pharmacology) c
2c Stanford University, 2007.
21 7 MD 2f (Medical Scientist Training Program) c
2c Stanford University, 2010.
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Permanent link21 7 BA 1e (Molecular Biology) c
2d Princeton University, 2001.
21 8 PhD 40 (Chemical & Systems Biology / Molecular Pharmacology) c
2c Stanford University, 2007.
21 7 MD 2f (Medical Scientist Training Program) c
2c Stanford University, 2010.
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25b 1) DNA-LNPs: They developed the first safe & effective DNA-loaded lipid nanoparticles (DNA-LNPs; PMIDs 39910195 & 40789922), and are using these to treat a variety of chronic diseases. DNA-LNPs treat 3 groups of diseases: a) Monogenic diseases not well served by AAV or CRISPR gene editing, such as cystic fibrosis, hemophilia A, and neurofibromatosis. b) Rare non-monogenic diseases such as pulmonary hypertension and bronchopulmonary dysplasia. c) DNA-LNPs are uniquely useful for common chronic diseases, including: obesity, diabetes, atherosclerosis, fibrosis, arthritis, and many more.
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eb 2) mRNA-LNPs for acute critical illnesses: We have developed engineered LNPs to treat the diseases of the ICU, such as acute ischemic stroke and intracerebral hemorrhage, ARDS (acute respiratory distress syndrome) and sepsis.
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10c 3) Toxicology of nanomedicine and gene therapy: We have identified the mechanisms of side effects of LNPs, and then engineered solutions. These side effects include inflammation (innate immune system activation), complement activation, thrombosis, and more.
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b9 4) Disease dynamics: We use tools from complexity science and statistical physics to understand diseases as dynamical systems, starting with a 2025 paper in Cell (PMID 40516526)
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Description of Clinical Expertise
c0 Dr. Brenner attends in the Medical Intensive Care Unit (MICU) at the Hospital of the University of Pennsylvania. He is board certified and fellowship trained in critical care.62
Description of Other Expertise
56 Dr. Brenner teaches nanomedicine and medical entrepreneurship at Penn.65
Description of Research Expertise
cb The Brenner Lab (brennerbioengineeringlab.com) uses the tools of nanotechnology and nanomedicine to create new gene therapy / genetic medicine therapies. Their research is in 4 buckets:8
25b 1) DNA-LNPs: They developed the first safe & effective DNA-loaded lipid nanoparticles (DNA-LNPs; PMIDs 39910195 & 40789922), and are using these to treat a variety of chronic diseases. DNA-LNPs treat 3 groups of diseases: a) Monogenic diseases not well served by AAV or CRISPR gene editing, such as cystic fibrosis, hemophilia A, and neurofibromatosis. b) Rare non-monogenic diseases such as pulmonary hypertension and bronchopulmonary dysplasia. c) DNA-LNPs are uniquely useful for common chronic diseases, including: obesity, diabetes, atherosclerosis, fibrosis, arthritis, and many more.
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eb 2) mRNA-LNPs for acute critical illnesses: We have developed engineered LNPs to treat the diseases of the ICU, such as acute ischemic stroke and intracerebral hemorrhage, ARDS (acute respiratory distress syndrome) and sepsis.
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10c 3) Toxicology of nanomedicine and gene therapy: We have identified the mechanisms of side effects of LNPs, and then engineered solutions. These side effects include inflammation (innate immune system activation), complement activation, thrombosis, and more.
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b9 4) Disease dynamics: We use tools from complexity science and statistical physics to understand diseases as dynamical systems, starting with a 2025 paper in Cell (PMID 40516526)
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283 Omo-Lamai S, Wang Y, Patel MN, Milosavljevic A, Zuschlag D, Poddar S, Wu J, Wang L, Dong F, Espy C, Majumder A, Essien EO, Shen M, Channer B, Papp TE, Tobin M, Maheshwari R, Jeong S, Patel S, Shah A, Murali S, Chase LS, Zamora ME, Arral ML, Marcos-Contreras OA, Myerson JW, Hunter CA, Discher D, Gaskill PJ, Tsourkas A, Muzykantov VR, Brodsky I, Shin S, Whitehead KA, Parhiz H, Katzen J, Miner JJ, Trauner D, Brenner JS.: Limiting endosomal damage sensing reduces inflammation triggered by lipid nanoparticle endosomal escape. Nat Nanotechnol 20(9): 1285-1297, Aug 2025.
25c Shuvaev VV, Tam YK, Lee BW, Myerson JW, Herbst A, Kiseleva RY, Glassman PM, Parhiz H, Alameh MG, Pardi N, Muramatsu H, Shuvaeva TI, Arguiri E, Marcos-Contreras OA, Hood ED, Brysgel TV, Nong J, Papp TE, Eaton DM, Riley R, Palanki R, Musunuru K, Brenner JS, Mitchell MJ, Ferrari VA, Mui BL, Semple SC, Weppler SA, Atluri P, Margulies KB, Weissman D, Muzykantov VR.: Systemic delivery of biotherapeutic RNA to the myocardium transiently modulates cardiac contractility in vivo. Proc Natl Acad Sci U S A 122(29): e2409266122, Jul 2025.
160 Roth AM, D'Angelo AK, Gordon D, Cocchiaro B, Lingamoorthy A, Laurano R, Salzman M, Brenner JS, Baston C.: Use of a Shoulder-Mounted Wearable Sensor Prototype Designed to Detect Opioid-Related Overdose: A Qualitative User Experience Study. J Med Internet Res 27: e73566, Jul 2025.
ee Patel MN, Tiwari S, Brenner JS.: Perspective: Advancing safe and effective DNA therapeutics using bioactive lipid nanoparticles. Mol Ther 33(6): 2324-2325, Jun 2025.
22c Tursi NJ, Tiwari S, Bedanova N, Kannan T, Parzych E, Okba N, Liaw K, Sárközy A, Livingston C, Trullen MI, Gary EN, Vadovics M, Laenger N, Londregan J, Khan MS, Omo-Lamai S, Muramatsu H, Blatney K, Hojecki C, Machado V, Maricic I, Smith TRF, Humeau LM, Patel A, Kossenkov A, Brenner JS, Allman D, Krammer F, Pardi N, Weiner DB.: Modulation of lipid nanoparticle-formulated plasmid DNA drives innate immune activation promoting adaptive immunity. Cell Rep Med 6(4): 102035, Apr 2025.
11b Zhang Z, Xu C, Gong N, Qing G, Zhang Y, Shi Y, Brenner JS, Li F, Xu FJ, Liang XJ.: An antigen-capturing and lymph node-targeting nanoparticle for cancer immunotherapy. J Control Release 379: 993-1005, Mar 2025.
17d Patel MN, Tiwari S, Wang Y, O'Neill S, Wu J, Omo-Lamai S, Espy C, Chase LS, Majumder A, Hoffman E, Shah A, Sárközy A, Katzen J, Pardi N, Brenner JS: Safer non-viral DNA delivery using lipid nanoparticles loaded with endogenous anti-inflammatory lipids. Nat Biotechnol Feb 2025 Notes: online ahead of print.
16c Zaleski MH, Chase LS, Hood ED, Wang Z, Nong J, Espy CL, Zamora ME, Wu J, Morrell LJ, Muzykantov VR, Myerson JW, Brenner JS.: Conjugation Chemistry Markedly Impacts Toxicity and Biodistribution of Targeted Nanoparticles, Mediated by Complement Activation. Adv Mater 37(5): e2409945, Dec 2024.
1bd Zaleski MH, Omo-Lamai S, Nong J, Chase LS, Myerson JW, Glassman PM, Lee F, Reyes-Esteves S, Wang Z, Patel MN, Peshkova AD, Komatsu H, Axelsen PH, Muzykantov VR, Marcos-Contreras OA, Brenner JS.: Nanocarriers' repartitioning of drugs between blood subcompartments as a mechanism of improving pharmacokinetics, safety, and efficacy. J Control Release 374: 425-440, Oct 2024.
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Selected Publications
ee Patel MN, Tiwari S, Brenner JS.: Preparation and Characterization of Lipid Nanoparticles Co-loaded With DNA and Nitro-Oleic Acid. Bio Protoc 15(18): e5450, Sep 2025.283 Omo-Lamai S, Wang Y, Patel MN, Milosavljevic A, Zuschlag D, Poddar S, Wu J, Wang L, Dong F, Espy C, Majumder A, Essien EO, Shen M, Channer B, Papp TE, Tobin M, Maheshwari R, Jeong S, Patel S, Shah A, Murali S, Chase LS, Zamora ME, Arral ML, Marcos-Contreras OA, Myerson JW, Hunter CA, Discher D, Gaskill PJ, Tsourkas A, Muzykantov VR, Brodsky I, Shin S, Whitehead KA, Parhiz H, Katzen J, Miner JJ, Trauner D, Brenner JS.: Limiting endosomal damage sensing reduces inflammation triggered by lipid nanoparticle endosomal escape. Nat Nanotechnol 20(9): 1285-1297, Aug 2025.
25c Shuvaev VV, Tam YK, Lee BW, Myerson JW, Herbst A, Kiseleva RY, Glassman PM, Parhiz H, Alameh MG, Pardi N, Muramatsu H, Shuvaeva TI, Arguiri E, Marcos-Contreras OA, Hood ED, Brysgel TV, Nong J, Papp TE, Eaton DM, Riley R, Palanki R, Musunuru K, Brenner JS, Mitchell MJ, Ferrari VA, Mui BL, Semple SC, Weppler SA, Atluri P, Margulies KB, Weissman D, Muzykantov VR.: Systemic delivery of biotherapeutic RNA to the myocardium transiently modulates cardiac contractility in vivo. Proc Natl Acad Sci U S A 122(29): e2409266122, Jul 2025.
160 Roth AM, D'Angelo AK, Gordon D, Cocchiaro B, Lingamoorthy A, Laurano R, Salzman M, Brenner JS, Baston C.: Use of a Shoulder-Mounted Wearable Sensor Prototype Designed to Detect Opioid-Related Overdose: A Qualitative User Experience Study. J Med Internet Res 27: e73566, Jul 2025.
ee Patel MN, Tiwari S, Brenner JS.: Perspective: Advancing safe and effective DNA therapeutics using bioactive lipid nanoparticles. Mol Ther 33(6): 2324-2325, Jun 2025.
22c Tursi NJ, Tiwari S, Bedanova N, Kannan T, Parzych E, Okba N, Liaw K, Sárközy A, Livingston C, Trullen MI, Gary EN, Vadovics M, Laenger N, Londregan J, Khan MS, Omo-Lamai S, Muramatsu H, Blatney K, Hojecki C, Machado V, Maricic I, Smith TRF, Humeau LM, Patel A, Kossenkov A, Brenner JS, Allman D, Krammer F, Pardi N, Weiner DB.: Modulation of lipid nanoparticle-formulated plasmid DNA drives innate immune activation promoting adaptive immunity. Cell Rep Med 6(4): 102035, Apr 2025.
11b Zhang Z, Xu C, Gong N, Qing G, Zhang Y, Shi Y, Brenner JS, Li F, Xu FJ, Liang XJ.: An antigen-capturing and lymph node-targeting nanoparticle for cancer immunotherapy. J Control Release 379: 993-1005, Mar 2025.
17d Patel MN, Tiwari S, Wang Y, O'Neill S, Wu J, Omo-Lamai S, Espy C, Chase LS, Majumder A, Hoffman E, Shah A, Sárközy A, Katzen J, Pardi N, Brenner JS: Safer non-viral DNA delivery using lipid nanoparticles loaded with endogenous anti-inflammatory lipids. Nat Biotechnol Feb 2025 Notes: online ahead of print.
16c Zaleski MH, Chase LS, Hood ED, Wang Z, Nong J, Espy CL, Zamora ME, Wu J, Morrell LJ, Muzykantov VR, Myerson JW, Brenner JS.: Conjugation Chemistry Markedly Impacts Toxicity and Biodistribution of Targeted Nanoparticles, Mediated by Complement Activation. Adv Mater 37(5): e2409945, Dec 2024.
1bd Zaleski MH, Omo-Lamai S, Nong J, Chase LS, Myerson JW, Glassman PM, Lee F, Reyes-Esteves S, Wang Z, Patel MN, Peshkova AD, Komatsu H, Axelsen PH, Muzykantov VR, Marcos-Contreras OA, Brenner JS.: Nanocarriers' repartitioning of drugs between blood subcompartments as a mechanism of improving pharmacokinetics, safety, and efficacy. J Control Release 374: 425-440, Oct 2024.
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