Drew Weissman

Verified

University of Pennsylvania · Rehabilitation Medicine

Active 1961–2026

h-index80

Citations33.4k

Papers345202 last 5y

Funding$18.6M1 active

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About

Drew Weissman, M.D., Ph.D., is the Roberts Family Professor in Vaccine Research at the University of Pennsylvania Perelman School of Medicine. He serves as the Director of Vaccine Research in the Infectious Diseases Division and is the Director of the Institute for RNA Innovation. His laboratory focuses on the study of RNA and innate immune system biology, applying these findings to vaccine research and gene therapy. His research projects include the development of mRNA-based vaccine delivery systems to promote broad immune responses, the creation of new HIV envelope immunogens capable of inducing broad responses and cross-reactive neutralizing antibodies, and the investigation of proteins on dendritic cells, macrophages, and epithelial cells that bind HIV envelope, to understand their role in HIV genital tract infection.

Research topics

Biology
Immunology
Virology
Genetics
Medicine
Computer Science
Internal medicine
Biochemistry
Computational biology
Cell biology
Chemistry
Telecommunications
Cancer research
Physics
Nanotechnology
Molecular biology
Materials science

Selected publications

296a REVERSAL OF END-STAGE LIVER DISEASE BY TREATMENT WITH HNF4A-MRNA-LNP
Gastroenterology · 2026-05-01
articleSenior author
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296a REVERSAL OF END-STAGE LIVER DISEASE BY TREATMENT WITH HNF4A-MRNA-LNP
Gastrointestinal Endoscopy · 2026-05-01
articleSenior author
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Prodrug-tethered lipid nanoparticles for synergistic messenger RNA cancer immunotherapy
Nature Nanotechnology · 2026-03-01
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Efficacy and immunological correlates of an mRNA-LNP vaccine for protection against an emerging rickettsial pathogen
Emerging Microbes & Infections · 2026-03-13
articleOpen access
infection, with significant humoral immune responses including infection-neutralizing antibodies, balanced Th1/Th2 response, and antigen-specific T helper and cytotoxic T cell activation. These data suggest that the mRNA-LNP approach is a viable strategy for developing efficient anti-rickettsial vaccines
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Hepatitis C virus modified S E2 F442NYT -mRNA-LNP candidate vaccine promotes helper CXCR5 + T cells
Journal of Virology · 2025-09-05 · 1 citations
articleOpen access
ABSTRACT T cells play an important role in initiating antibody responses by instructive signals of cell-cell contacts and secretion of soluble cytokines as mediators. We investigated the role of the modified soluble E2 (sE2 F442NYT ) antigen from hepatitis C virus (HCV) on healthy human peripheral blood mononuclear cell (PBMC)-derived immune cells or immunized mouse cells to understand the mechanisms of immune regulation by the candidate vaccine antigen. HCV E2 and E2 F442NYT displayed a role in inducing type 17 T-helper cell (Th17) phenotype, as indicated by interleukin-17 (IL-17) expression and signal transducer and activator of transcription 3 (Stat3) phosphorylation. The spleen cells from sE2-mRNA-lipid nanoparticles (LNPs) or sE2 F442NYT -mRNA-LNP-immunized mice exhibited similar IL-17A mRNA levels, and Th17 (CXCR3 − CCR6 + ) cells in CD4 + CD44 + spleen cells, supporting both sE2 and modified sE2 F442NYT - induced Th17 polarization. Immunohistochemical and multiplex immunofluorescence imaging studies revealed abundant CD4 + CXCR5 + T cells co-localized with BCL6 in sE2 F442NYT -mRNA-LNP immunized mouse spleen cells than unmodified sE2-mRNA-LNP immunized animals, suggesting sE2 F442NYT induces stronger follicular helper T cell generation. We previously demonstrated increased total IgG production and isotype switching from IgG1 to IgG2a and IgG2b in sE2 442NYT immunized mice. The stronger B and T cell responses observed from modified sE2 F442NYT support the overall in vivo outcome of the study toward a higher B helper T cell generation from sE2 F442NYT -mRNA-LNP immunization as compared to unmodified sE2-mRNA-LNP. IMPORTANCE The study will help rationalize HCV vaccine antigen selection for an effective immune response. Extension by additional strategies may be useful to direct stronger B helper T cell generation for prolonged vaccine-associated protection.
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Harnessing mRNA-lipid nanoparticles as innovative therapies for autoimmune diseases
Molecular Therapy — Methods & Clinical Development · 2025-08-18 · 12 citations
reviewOpen access
chimeric antigen T cell therapies. To successfully advance this promising class of therapies to the clinic, key challenges must be addressed, such as mitigating unwanted inflammation caused by LNPs, overcoming biological barriers to delivery, and ensuring the long-term safety of mRNA-LNPs specifically in autoimmune contexts. Through their modular design, flexible application, and potential for cost-effective production, mRNA-LNP therapies offer exciting clinical potential to transform the management of autoimmune diseases.
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In vivo reprogramming of cytotoxic effector CD8 + T cells via fractalkine-conjugated mRNA-LNP
bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-30 · 1 citations
preprintOpen access
Abstract Selective in vivo reprogramming of cytotoxic effector CD8 + T (T eff ) cells holds tremendous promise as a therapeutic tool but has not yet been accomplished. Here, we demonstrate that fractalkine-conjugated mRNA lipid nanoparticles (mRNA-LNP) can specifically target and deliver mRNA to CX3CR1 + T eff cells in vitro and in vivo. In mice, fractalkine-conjugated LNP target up to 90% of blood and splenic T eff cells, and delivery of IL-2-encoding mRNA to T eff cells enables robust exogenous IL-2 secretion. In rhesus macaques, fractalkine-conjugated mRNA-LNP target up to ∼100% of peripheral blood T eff cells and delivery of CD62L-mRNA enables transient CD62L expression. Collectively, these data demonstrate the potential of natural receptor ligand-based targeting of mRNA-LNP for effective and efficient transient in vivo modification of T eff cells.
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mRNA-LNP vaccine encoding the Plasmodium vivax circumsporozoite protein is highly immunogenic and confers protection in mice
Molecular Therapy — Nucleic Acids · 2025-07-30 · 2 citations
articleOpen access
pre-erythrocytic stage infection.
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An influenza HA mRNA-LNP vaccine induces potent responses in newborn nonhuman primates that enhance protection from challenge
npj Vaccines · 2025-12-26 · 1 citations
articleOpen access
Influenza virus infection poses a significant health risk to newborns, with this population experiencing higher hospitalization and mortality rates compared to older children. The heightened vulnerability of this age group results from a combination of an altered immune system and lack of a licensed vaccine for children under six months of age. mRNA-LNP vaccines have shown remarkable efficacy, including the capacity to induce antibodies in poorly responding populations. This makes them a promising candidate for addressing the unique immunological environment of newborns. Here, we leveraged the close immunological and physiological similarity of NHP to evaluate the efficacy of an influenza hemagglutinin mRNA-LNP vaccine in newborns. Our findings show the HA mRNA-LNP vaccine elicits robust, multi-functional antibody responses in newborn NHP that result in significantly reduced viral load and disease severity following challenge. These results highlight the potential of mRNA-based vaccines as a transformative approach to protect the vulnerable newborn population against influenza. Continued development and optimization of this platform could address the critical gap in influenza virus and other pathogen vaccine coverage for infants under six months of age.
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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.
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