HYBRID EVENT: You can participate in person at Rome, Italy or Virtually from your home or work.
A C Matin, Speaker at Pharmaceutical Conferences
Stanford University, United States
Title : mRNA-based systemically delivered directed gene therapy using nanomaterials


The presentation focuses on systemically administered targeted gene therapy using mRNA instead of DNA; why the former is superior for this purpose will be discussed. Lipid nanoparticles (LNPs) and, more recently, extracellular vesicles (EVs, aka exosomes) have proven effective vectors. An example of LNP-mediated directed mRNA delivery is that of the Cas9 gene for editing of PTEN by the CRISPR/Cas system. Also, an mRNA-LNP drug, NTLA-2001, is in a clinical trial for treating transthyretin amyloidosis. EVs are nature’s own antigen delivery system, posing minimal immunogenicity/toxicity risk and their surface integrins confer intrinsic tissue tropism. They have been engineered to display targeting moieties, which are fused to EV anchor domains. The emphasis here will be on the lactadherin C1-C2 anchor domain (which binds to the EV surface) and its fusion to a high-affinity anti-HER2 scFv, resulting in HER2 receptor targeting EVs. These were loaded with mRNA that encodes the enzyme HChrR6, which can activate several prodrugs, including CNOB and CB1954 (tretazicar). (The loaded and targeted EVs are called ‘EXODEPTs’.) Systemic delivery of EXODEPTs along with either CNOB or tretazicar resulted in the killing of HER2+ breast cancer xenografts in mice without any off-target effects, indicating gene delivery exclusively to cancer. Attaining specific tumor targeting and loading of the EVs with the HChrR6 mRNA was greatly facilitated by the fact that the activated drug of CNOB, MCHB, is highly fluorescent and can be visualized non-invasively in living mice. Tretazicar (whose activation could also be visualized vicariously by MCHB) was effective at its safe dose; the EVs needed to be delivered only twice, and there were no side effects. Thus, the results augment the clinical transfer potential of this regimen. Examples of EV targeting using other anchor proteins, e.g., Lamp2b and CD47, will also be briefly discussed. As the EV anchor domains can be fused to other targeting moieties, the approach is generic for specific gene delivery also in other diseases.


He is a professor of Microbiology and Immunology from Stanford University School of Medicine. He was born in USA and completed his PhD in the year 1969 in the field of microbiology from University of California, Los Angeles. He  is having a teaching knowledge of around 55 years. He is an active member for many microbiological and immunological societies and association. He received the Fulbright Scholar award in the year 1964-1971. He is the author for 142 publications along with few patents. He has been a part of many scientific conferences during his teaching and educational career. He had received the funding from reputed organization for his research work. His current research interest includes immunology, Microbiology, Cancer, Genetics studies etc. Currently he is working on Exosome (EV) project and also on the Extension of the ongoing antibiotic work.