About

Mohamad Gabriel Alameh, Ph.D., is an Assistant Professor of Pathology and Laboratory Medicine at the University of Pennsylvania's Perelman School of Medicine. He is the Director of the Engineered mRNA and Targeted Nanomedicine Core, where he addresses infrastructural barriers to clinical and translational research in gene therapy, vaccine development, stem cell reprogramming, and other non-viral gene therapy applications by designing and providing high-quality in vitro transcribed messenger RNA (IVT-mRNA) and lipid nanoparticles. He has established over 100 academic and industrial collaborations through this core, generating significant profit. His research expertise encompasses the development of novel lipid nanoparticles, understanding their adjuvant activity, and designing mRNA-based vaccines for various pathogens including C. difficile and SARS-CoV-2. He has elucidated the effects of different parameters on chitosan-siRNA nanoparticle formation, demonstrated the adjuvant activity of ionizable lipids through cytokine induction, and contributed to the development of multivalent mRNA vaccines that provide broad protection in animal models. Dr. Alameh has also contributed to the design and conduction of multiple vaccine studies and has been involved in licensing negotiations with major pharmaceutical companies. His work has led to several provisional patent applications and the movement of vaccine platforms into phase I clinical trials.

Research topics

• Biology
• Virology
• Immunology
• Computer Science
• Internal medicine
• Chemistry
• Materials science
• Genetics
• Biochemistry
• Computational biology
• Physics
• Nanotechnology
• Medicine
• Telecommunications

Selected publications

• Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination

  Science Immunology · 2022 · 362 citations

  • Immunology
  • Virology
  • Biology

  SARS-CoV-2 mRNA vaccination induces robust humoral and cellular immunity in the circulation; however, it is currently unknown whether it elicits effective immune responses in the respiratory tract, particularly against variants of concern (VOCs), including Omicron. We compared the SARS-CoV-2 S-specific total and neutralizing antibody responses, and B and T cell immunity, in the bronchoalveolar lavage fluid (BAL) and blood of COVID-19-vaccinated individuals and hospitalized patients. Vaccinated individuals had significantly lower levels of neutralizing antibody against D614G, Delta (B.1.617.2), and Omicron BA.1.1 in the BAL compared with COVID-19 convalescents despite robust S-specific antibody responses in the blood. Furthermore, mRNA vaccination induced circulating S-specific B and T cell immunity, but in contrast to COVID-19 convalescents, these responses were absent in the BAL of vaccinated individuals. Using a mouse immunization model, we demonstrated that systemic mRNA vaccination alone induced weak respiratory mucosal neutralizing antibody responses, especially against SARS-CoV-2 Omicron BA.1.1 in mice; however, a combination of systemic mRNA vaccination plus mucosal adenovirus-S immunization induced strong neutralizing antibody responses not only against the ancestral virus but also the Omicron BA.1.1 variant. Together, our study supports the contention that the current COVID-19 vaccines are highly effective against severe disease development, likely through recruiting circulating B and T cell responses during reinfection, but offer limited protection against breakthrough infection, especially by the Omicron sublineage. Hence, mucosal booster vaccination is needed to establish robust sterilizing immunity in the respiratory tract against SARS-CoV-2, including infection by the Omicron sublineage and future VOCs.

  DOI

• Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses

  Immunity · 2021 · 704 citations

  1st authorCorresponding
  • Biology
  • Immunology
  • Virology
  PublisherOA PDFDOI

• Scalable mRNA and siRNA Lipid Nanoparticle Production Using a Parallelized Microfluidic Device

  Nano Letters · 2021 · 288 citations

  • Computer Science
  • Nanotechnology
  • Computational biology

  A major challenge to advance lipid nanoparticles (LNPs) for RNA therapeutics is the development of formulations that can be produced reliably across the various scales of drug development. Microfluidics can generate LNPs with precisely defined properties, but have been limited by challenges in scaling throughput. To address this challenge, we present a scalable, parallelized microfluidic device (PMD) that incorporates an array of 128 mixing channels that operate simultaneously. The PMD achieves a >100× production rate compared to single microfluidic channels, without sacrificing desirable LNP physical properties and potency typical of microfluidic-generated LNPs. In mice, we show superior delivery of LNPs encapsulating either Factor VII siRNA or luciferase-encoding mRNA generated using a PMD compared to conventional mixing, with a 4-fold increase in hepatic gene silencing and 5-fold increase in luciferase expression, respectively. These results suggest that this PMD can generate scalable and reproducible LNP formulations needed for emerging clinical applications, including RNA therapeutics and vaccines.

  DOI

• D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization

  Cell Host & Microbe · 2020 · 353 citations

  • Biology
  • Virology
  • Genetics
  DOI

Frequent coauthors

• Drew Weissman

  University of Pennsylvania

  115 shared

• Michael J. Mitchell

  University of Pennsylvania

  61 shared

• Ying K. Tam

  Acuitas Therapeutics (Canada)

  31 shared

• Xuexiang Han

  Nanjing University of Chinese Medicine

  24 shared

• Paulo J.C. Lin

  Acuitas Therapeutics (Canada)

  18 shared

• Ningqiang Gong

  University of Pennsylvania

  17 shared

• Jie Sun

  China Tourism Academy

  16 shared

• Garima Dwivedi

  Developmental Studies Center

  16 shared

Education

• PhD, Biomedical engineering

  Polytechnique Montréal

  2017

Awards & honors

• Provisional patent applications for chitosan based siRNA del…
• Provisional patent applications for C. difficile and VLP bas…

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