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Drew Weissman, M.D., Ph.D.

Roberts Family Professor in Vaccine Research, Co-Director of the Penn Center of AIDS Research Immunology Core, and Director of Vaccine Research in the Infectious Diseases Division
University of Pennsylvania
Telephone: (215) 573-8491
Email: dreww@pennmedicine.upenn.edu

Drew Weissman, M.D., Ph.D. is a professor of Medicine at the Perelman School of Medicine, University of Pennsylvania.  He received his graduate degrees from Boston University School of Medicine.  Dr. Weissman, in collaboration with Dr. Katalin Karikó, discovered the ability of modified nucleosides in RNA to suppress activation of innate immune sensors and increase the translation of mRNA containing certain modified nucleosides.  The nucleoside-modified mRNA-lipid nanoparticle vaccine platform Dr. Weissman’s lab created is used in the first 2 approved COVID-19 vaccines by Pfizer/BioNTech and Moderna.  They continue to develop other vaccines that induce potent antibody and T cell responses with mRNA–based vaccines.  Dr. Weissman’s lab also develops methods to replace genetically deficient proteins, edit the genome, and specifically target cells and organs with mRNA-LNPs, including lung, heart, brain, CD4+ cells, all T cells, and bone marrow stem cells.

Pseudouridine
N1-methyl-pseudouridine-5'-triphosphate

The Weissman lab studies nucleoside-modified mRNA and lipid nanoparticle (LNP) therapeutics.  Their findings of the safety and efficacy of nucleoside-modified mRNA have moved this technology to the forefront of new therapeutics.  Their technology is used in the first 2 FDA approved COVID-19 vaccines.  The lab broadly studies 2 directions of mRNA research: 1) vaccines and 2) mRNA protein therapeutics, such as monoclonal antibody delivery and gene editing.  While interested in developing new therapeutics, the lab’s main interest is basic science research.  Any therapeutic approach being studied always involves extensive basic science investigation to understand mechanisms.

The lab has an extensive portfolio of vaccine studies, including viral, bacterial, parasitic, oncologic, and allergic diseases.  A main interest in the lab is the development of vaccines for difficult diseases where previous vaccine strategies have failed, such as genital herpes, HIV, HCV, malaria, and tuberculosis.  We work with experts in the fields for each vaccine that allows the use of optimal animal model systems and assays to measure effectiveness.  New vaccines that will be effective against drifted and pandemic influenza strains, pan-influenza, and all coronaviruses capable of crossing over from bats, pan-coronavirus, are being developed.  In addition, novel vaccines that will be effective at treating common food and environmental allergies are being evaluated.

Protein therapeutics is the fastest growing element of the pharmaceutical industry.  We believe nucleoside-modified mRNA offers a superior approach to deliver such proteins, as the host is the factory that makes the proteins.  Numerous nucleoside-modified mRNAs encoding therapeutic proteins, including monoclonal antibodies, acute care therapies, and genetically deficient proteins are ongoing.  Nucleoside-modified mRNA offers many advantages for gene therapy, including transient and controllable activity.  The main impediment to in vivo gene therapy is the need to specifically target the therapy to the cells of interest.  We have developed new technology that specifically delivers LNPs to: lungs, heart, brain, CD4+ cells, all T cells, and bone marrow stem cells.  This targeting allows the delivery of gene editing systems to the specific cells and organs that require gene manipulation with simple intravenous injections of targeted mRNA-LNPs.

fluorescent mice
Mice expressing proteins encoded by mRNA-LNPs

The goals of the Weissman lab are multifold.  We seek to develop new nucleoside-modified mRNA-LNP platforms for vaccines, protein therapeutics, and gene therapy.  This includes new platforms for vaccines and their application to many different types of diseases.  To change and advance protein therapeutics by more safely and efficiently delivering proteins and extending this to therapies that require intracellular protein activity.  To develop gene therapies using newly developed methods to alter the genome delivered by nucleoside-modified mRNA and delivered with targeting LNPs, thus allowing simple intravenous administration to achieve in vivo gene modification.  Finally, we extensively investigate the basic science and mechanisms for our new therapies, which allows careful and directed optimization to improve them.

Selected Publications

  1. Rurik JG, Tombácz I, Yadegari A, Méndez Fernández PO, Shewale SV, Li L, Kimura T, Soliman OY, Papp TE, Tam YK, Mui BL, Albelda SM, Puré E, June CH, Aghajanian H, Weissman D, Parhiz H, Epstein JA.: CAR T cells produced in vivo to treat cardiac injury. Science 375: 91-96, Jan 2022.
  2. Han X, Zhang H, Butowska K, Swingle KL, Alameh MG, Weissman D, Mitchell MJ.: An ionizable lipid toolbox for RNA delivery. Nat Commun 12: 7233, Dec 2021.
  3. Alameh MG, Tombácz I, Bettini E, Lederer K, Sittplangkoon C, Wilmore JR, Gaudette BT, Soliman OY, Pine M, Hicks P, Manzoni TB, Knox JJ, Johnson JL, Laczkó D, Muramatsu H, Davis B, Meng W, Rosenfeld AM, Strohmeier S, Lin PJC, Mui BL, Tam YK, Karikó K, Jacquet A, Krammer F, Bates P, Cancro MP, Weissman D, Luning Prak ET, Allman D, Locci M, Pardi N.: Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses. Immunity 54: 2877-2892, Dec 2021.
  4. Awasthi S, Knox JJ, Desmond A, Alameh MG, Gaudette BT, Lubinski JM, Naughton A, Hook LM, Egan KP, Tam YK, Pardi N, Allman D, Luning Prak ET, Cancro MP, Weissman D, Cohen GH, Friedman HM.: Trivalent nucleoside-modified mRNA vaccine yields durable memory B cell protection against genital herpes in preclinical models. J Clin Invest 131: e152310, Dec 2021.
  5. Parhiz H, Brenner JS, Patel P, Papp TE, Shahnawaz H, Li Q, Shi R, Zamora M, Yadegari A, Marcos-Contreras OA, Natesan A, Pardi N, Shuvaev VV, Kiseleva R, Myerson J, Uhler T, Riley RS, Han X, Mitchell MJ, Lam K, Heyes J, Weissman D, Muzykantov V.: Added to pre-existing inflammation, mRNA-lipid nanoparticles induce inflammation exacerbation (IE). J Control Release Dec 2021.
  6. Matias J, Kurokawa C, Sajid A, Narasimhan S, Arora G, Diktas H, Lynn GE, DePonte K, Pardi N, Valenzuela JG, Weissman D, Fikrig E.: Tick immunity using mRNA, DNA and protein-based Salp14 delivery strategies. Vaccine 39: 7661-7668, Dec 2021.
  7. Zhang D, Atochina-Vasserman EN, Maurya DS, Liu M, Xiao Q, Lu J, Lauri G, Ona N, Reagan EK, Ni H, Weissman D, Percec V.: Targeted Delivery of mRNA with One-Component Ionizable Amphiphilic Janus Dendrimers. J Am Chem Soc 143: 17975-17982, Nov 2021.
  8. Melamed JR, Hajj KA, Chaudhary N, Strelkova D, Arral ML, Pardi N, Alameh MG, Miller JB, Farbiak L, Siegwart DJ, Weissman D, Whitehead KA.: Lipid nanoparticle chemistry determines how nucleoside base modifications alter mRNA delivery. J Control Release 341: 206-214, Nov 2021.
  9. Swingle KL, Billingsley MM, Bose SK, White B, Palanki R, Dave A, Patel SK, Gong N, Hamilton AG, Alameh MG, Weissman D, Peranteau WH, Mitchell MJ.: Amniotic fluid stabilized lipid nanoparticles for in utero intra-amniotic mRNA delivery. J Control Release 341: 616-633, Nov 2021.
  10. Sajid A, Matias J, Arora G, Kurokawa C, DePonte K, Tang X, Lynn G, Wu MJ, Pal U, Strank NO, Pardi N, Narasimhan S, Weissman D, Fikrig E.: mRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent. Sci Transl Med 13: eabj9827, Nov 2021.