A5067992777- SARS-CoV-2 and COVID-19 Research
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- Animal Virus Infections Studies
- Viral gastroenteritis research and epidemiology
- Virus-based gene therapy research
- HIV Research and Treatment
- Influenza Virus Research Studies
- Immune Cell Function and Interaction
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- COVID-19 Clinical Research Studies
- Liver physiology and pathology
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Viral Infections and Vectors
- Viral Infections and Immunology Research
- vaccines and immunoinformatics approaches
- Liver Disease Diagnosis and Treatment
- Pancreatic function and diabetes
- Respiratory viral infections research
- Viral Infections and Outbreaks Research
- Vector-borne infectious diseases
- CRISPR and Genetic Engineering
University of Pennsylvania
2016-2025
Philadelphia University
2024
California University of Pennsylvania
2024
Broad Institute
2023
Stanford University
2023
Jackson Memorial Hospital
2023
Scripps Research Institute
2023
Boston Children's Museum
2023
Boston Children's Hospital
2023
New York Academy of Sciences
2023
T follicular helper (Tfh) cells are required to develop germinal center (GC) responses and drive immunoglobulin class switch, affinity maturation, long-term B cell memory. In this study, we characterize a recently developed vaccine platform, nucleoside-modified, purified mRNA encapsulated in lipid nanoparticles (mRNA-LNPs), that induces high levels of Tfh GC cells. Intradermal vaccination with nucleoside-modified mRNA-LNPs encoding various viral surface antigens elicited polyfunctional,...
Abstract Monoclonal antibodies are one of the fastest growing classes pharmaceutical products, however, their potential is limited by high cost development and manufacturing. Here we present a safe cost-effective platform for in vivo expression therapeutic using nucleoside-modified mRNA. To demonstrate feasibility protective efficacy, mRNAs encoding light heavy chains broadly neutralizing anti-HIV-1 antibody VRC01 generated encapsulated into lipid nanoparticles. Systemic administration 1.4...
Abstract Most known pathogenic point mutations in humans are C•G to T•A substitutions, which can be directly repaired by adenine base editors (ABEs). In this study, we investigated the efficacy and safety of ABEs livers mice cynomolgus macaques for reduction blood low-density lipoprotein (LDL) levels. Lipid nanoparticle–based delivery mRNA encoding an ABE a single-guide RNA targeting PCSK9 , negative regulator LDL, induced up 67% editing (on average, 61%) 34% 26%) macaques. Plasma LDL levels...
Influenza viruses are respiratory pathogens of public health concern worldwide with up to 650,000 deaths occurring each year. Seasonal influenza virus vaccines employed prevent disease, but limited effectiveness. Development a universal vaccine the potential elicit long-lasting, broadly cross-reactive immune responses is necessary for reducing prevalence. In this study, we have utilized lipid nanoparticle-encapsulated, nucleoside-modified mRNA intradermally deliver combination conserved...
Abstract Currently available influenza virus vaccines have inadequate effectiveness and are reformulated annually due to viral antigenic drift. Thus, development of a vaccine that confers long-term protective immunity against antigenically distant strains is urgently needed. The highly conserved hemagglutinin (HA) stalk represents one the potential targets broadly protective/universal vaccines. Here, we evaluate potent candidate uses nucleoside-modified purified mRNA encoding full-length HA...
Seasonal influenza vaccines offer little protection against pandemic virus strains. It is difficult to create effective prepandemic because it uncertain which subtype will cause the next pandemic. In this work, we developed a nucleoside-modified messenger RNA (mRNA)-lipid nanoparticle vaccine encoding hemagglutinin antigens from all 20 known A subtypes and B lineages. This multivalent elicited high levels of cross-reactive subtype-specific antibodies in mice ferrets that reacted encoded...
A broad defense against SARS-like viruses Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third that has emerged as a serious human pathogen in past 20 years. Treatment strategies are broadly protective current and future coronaviruses needed. Martinez et al . take on this challenge by developing vaccines based chimeras of viral spike protein. The messenger RNA encode proteins composed domain modules from epidemic pandemic coronaviruses, well bat with potential to cross...
Lipid nanoparticle (LNP)-formulated nucleoside-modified mRNA vaccines have proven to be very successful in the fight against coronavirus disease 2019 (COVID-19) pandemic. They are effective, safe, and can produced large quantities. However, long-term storage of mRNA-LNP without freezing is still a challenge. Here, we demonstrate that mRNA-LNPs lyophilized, physicochemical properties lyophilized material do not significantly change for 12 weeks after at room temperature least 24 4°C....
Nucleoside-modified messenger RNA (mRNA)-lipid nanoparticles (LNPs) are the basis for first two EUA (Emergency Use Authorization) COVID-19 vaccines. The use of nucleoside-modified mRNA as a pharmacological agent opens immense opportunities therapeutic, prophylactic and diagnostic molecular interventions. In particular, mRNA-based drugs may specifically modulate immune cells, such T lymphocytes, immunotherapy oncologic, infectious other conditions. key challenge, however, is that cells...
An Ixodes scapularis saliva mRNA vaccine induces tick resistance and prevents Borrelia burgdorferi infection in guinea pigs.
Systemic messenger RNA (mRNA) delivery to organs outside the liver, spleen, and lungs remains challenging. To overcome this issue, we hypothesized that altering nanoparticle chemistry administration routes may enable mRNA-induced protein expression of reticuloendothelial system. Here, describe a strategy for delivering mRNA potently specifically pancreas using lipid nanoparticles. Our results show nanoparticles containing cationic helper lipids by intraperitoneal produces robust specific in...
Abstract During the COVID-19 pandemic, Pfizer-BioNTech and Moderna successfully developed nucleoside-modified mRNA lipid nanoparticle (LNP) vaccines. SARS-CoV-2 spike protein expressed by those vaccines are identical in amino acid sequence, but several key components distinct. Here, we compared effect of ionizable lipids, untranslated regions (UTRs), nucleotide composition two vaccines, focusing on delivery, antibody generation, long-term stability. We found that lipid, SM-102, Moderna’s...