About

Kiran Musunuru, MD, PhD, MPH, ML, MRA, is the Barry J. Gertz Professor for Translational Research at the University of Pennsylvania's Perelman School of Medicine. He serves as the Director of the Penn Cardiovascular Institute's Genetic and Epigenetic Origins of Disease Program and is the Scientific Director of the Penn Center for Inherited Cardiovascular Disease at the Hospital of the University of Pennsylvania. His research focuses on gene therapy, genome editing, and the genetic and epigenetic mechanisms underlying cardiovascular diseases. Dr. Musunuru has contributed to advancing therapeutic genome editing, including patient-specific in vivo gene editing to treat rare genetic diseases, and has been involved in moving therapeutic genome editing into clinical trials. His educational background includes degrees from Harvard College, The Rockefeller University, Weill-Cornell Medical College, Johns Hopkins Bloomberg School of Public Health, University of Pennsylvania Law School, and ongoing studies at the Perelman School of Medicine.

Research topics

• Genetics
• Biology
• Artificial Intelligence
• Computer Science
• Political Science
• Cell biology
• Engineering
• Computational biology
• Law
• Engineering ethics

Selected publications

• Developing a therapeutic in vivo prime editing strategy for MCAD deficiency

  Molecular Genetics and Metabolism · 2026-05-01

  article
  PublisherDOI

• CRISPR/Cas9 Screens Implicate RARA and SPNS1 in Doxorubicin Cardiotoxicity

  JACC CardioOncology · 2026-02-01

  articleOpen accessSenior author

  BACKGROUND: Doxorubicin (DOX) causes cardiotoxicity and heart failure in a significant fraction of patients, but the molecular etiology is poorly understood. OBJECTIVES: We adopted a functional genomics-based approach to probe the genetic basis for DOX-induced cardiotoxicity in an exhaustive and agnostic manner. METHODS: Genome-wide and targeted CRISPR/Cas9 screens were performed in immortalized cardiomyocytes and induced pluripotent stem cell-derived cardiomyocytes to identify genetic modifiers of DOX-induced cardiotoxicity. RESULTS: Our first screen revealed that loss of the Retinoic Acid Receptor Alpha gene (RARA) increased DOX-induced cell death. Conversely, pharmacological activation of RARA protein with tamibarotene reduced DOX-induced toxicity. RNA-Seq analysis showed that whereas DOX broadly suppressed expression of metabolic and mitochondrial genes, tamibarotene mitigated this effect. In a second screen, we interrogated processes involved in DOX uptake, transport, and efflux. Loss of lysosome homeostasis, exemplified by SPNS lysolipid transporter 1 (SPNS1) deficiency, led to DOX hyperaccumulation, suppression of autophagy, increased DNA damage, and increased cell death. In contrast, ribosome loss-of-function and nutrient deprivation significantly reduced DOX accumulation and toxicity. CONCLUSIONS: Our study identified numerous drug-gene interactions that illuminate mechanisms underlying DOX-induced cardiotoxicity and provide a technical framework for future functional genomics screens to nominate therapeutic targets and genetic biomarkers.

  PublisherDOI

• Correction of a recurrent pathogenic variant in methylmalonic acidemia using adenine base editing

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-15

  articleOpen accessCorresponding

  Abstract Methylmalonic acidemia (MMA) is a recessive genetic disease caused by variants in the MMUT (mitochondrial enzyme methylmalonyl–CoA mutase) gene or by defects in transport or metabolism of MMUT cofactor (5’ deoxyadenosylcobalamin), including variants in the MMAB gene. For the most recurrent pathogenic MMAB variant, c.556C>T (R186W), we identified a corrective editing strategy using adenine base editing. Deploying an adenine base editor mRNA and optimized hybrid guide RNA with lipid nanoparticles, we observed efficient in vitro corrective editing of the variant to wild-type, with minimized bystander editing and off-target editing in hepatocytes. These observations lay the groundwork for a gene editing therapy for patients with MMA resulting from at least one copy of the MMAB c.556C>T (R186W) variant, as well as a platform of similar therapies for patients with MMA caused by other variants amenable to adenine base editing.

  PublisherOA PDFDOI

• ASGCT’s 2025 breakthroughs in targeted in vivo gene editing: Meeting summary and insights

  Molecular Therapy · 2026-02-04

  articleSenior author
  PublisherDOI

• In vivo adenine base editing rescues brain biochemistry and improves motor deficits in a common phenylketonuria variant

  Molecular Therapy Advances · 2026-05-01

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  PublisherDOI

• Platform solutions for commercial challenges to expanding patient access and making gene editing sustainable

  Nature Biotechnology · 2025-07-01 · 4 citations

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  PublisherDOI

• Building Better Medicine: Translational Justice and the Quest for Equity in US Healthcare

  The American Journal of Bioethics · 2025-02-23 · 23 citations

  articleOpen access

  Despite considerable scientific progress and the evolution of regulatory pathways to ensure safety and efficacy, US healthcare continues to see increasing health disparities. This suggests that clinical translation in of itself cannot be the only measure of its own success, especially when the most marginalized patients, are neglected in the development and implementation of medical innovations. This raises the question of whether a system that is narrowly focused on technical achievement can meet the moral obligations of medicine and public health. We argue that traditional technocratic standards are failing to integrate normative considerations into biomedical translation. What is needed is a translational domain that moves beyond safety and efficacy toward anticipating how proposed technologies will be effective in society as it exists. We propose an additional metric of success: translational justice.

  PublisherOA PDFDOI

• Liver-directed base editing of ABCC6 prevents ectopic calcification in a variant-humanized mouse model of pseudoxanthoma elasticum

  Molecular Therapy — Nucleic Acids · 2025-11-11

  articleOpen access

  defects through adenine base editing may represent a novel, permanent therapy for the treatment of PXE.

  PublisherDOI

• Systemic delivery of biotherapeutic RNA to the myocardium transiently modulates cardiac contractility in vivo

  Proceedings of the National Academy of Sciences · 2025-07-16 · 10 citations

  articleOpen access

  Lipid nanoparticles (LNP) represent a versatile platform for improving delivery of therapeutic nucleic acids. Yet, delivery to the myocardium remains a formidable challenge due to local barriers in the heart and systemic hindrances. In particular, plasma apolipoprotein E (apoE) directs LNP to the liver, limiting potential extrahepatic delivery. Here, we report a cardiotropic LNP (cLNP), which within 30 min post–intravenous injection accumulates in the heart of ApoE knockout ( Apoe −/− ) mice. The findings were confirmed for Apoe −/− rats and for wild-type mice after siRNA-mediated plasma apoE ablation. To test cardiac-specific functional effects as a proof of concept, we used cLNP loaded with siRNA to ATP2A2, encoding the sarcoplasmic-endoplasmic reticulum Ca 2+ ATPase 2a (SERCA2A). This cardiomyocyte-specific protein is a key regulator of contractility and relaxation. Intravenous administration of cLNP/siRNA-ATP2A2 in Apoe −/− mice led to near-complete ablation of SERCA2A in the myocardium and a potent modulation of contractility of the cardiomyocytes obtained from these mice. In summary, cardiotropic nanocarriers may allow the delivery and effect of RNA and other agents to the myocardium. Achieving this unmet medical need promises new types of treatment for heart diseases, which remains the leading cause of death worldwide.

  PublisherDOI

• Measurement and clinical interpretation of CRISPR off-targets

  Nature Genetics · 2025-11-24 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

Recent grants

• OFF-TARGET RESOURCE CORE

  NIH · $35.0M · 2023–2028

• NIH Grant K99HL098364

  NIH · $275k · 2012

• Diagnosis, Prevention, And Treatment Of Cardiovascular Diseases With Genome Editing

  NIH · $5.7M · 2019–2026

• NIH Grant R01GM104464

  NIH · $1.3M · 2017

• Permanent alteration of PCSK9 in vivo genome editing

  NIH · $805k · 2017–2021

Frequent coauthors

• Christopher J. O’Donnell

  VA Boston Healthcare System

  124 shared

• Sekar Kathiresan

  Massachusetts General Hospital

  111 shared

• Wendy S. Post

  Johns Hopkins University

  107 shared

• Lisa R. Yanek

  106 shared

• Diane M. Becker

  Johns Hopkins University

  106 shared

• Qiong Yang

  Sun Yat-sen Memorial Hospital

  104 shared

• Alan R. Shuldiner

  Regeneron (United States)

  101 shared

• Kathleen A. Ryan

  University of Maryland, College Park

  101 shared

Awards & honors

• Barry J. Gertz Professor for Translational Research
• Director, Penn Cardiovascular Institute's Genetic and Epigen…
• Scientific Director, Penn Center for Inherited Cardiovascula…