Special seminar: Dr. Minh Le, National University of Singapore
Delivery of nucleic acid therapeutics using extracellular vesicles from red blood cells.
Tuesday May 23, 3-4pm (Koch Institute Luria Auditorium)
Minh T.N. LE, Ph.D.
Assistant Professor
Department of Pharmacology, and Institute for Digital Medicine, (secondary appointment: Department of Surgery, Cancer Program, Immunology Program and Nanomedicine Translational Research Program), Yong Loo Lin School of Medicine
National University of Singapore
Abstract: Despite their promise of therapeutic potency, many applications of nucleic acid-based drugs are currently limited by the poor delivery efficiency. As an emerging delivery platform for nanomedicine, extracellular vesicles (EVs) exhibit various advantageous features, including low immunogenicity and high biocompatibility. Moreover, the lipid bilayer that delimits each EV not only protects the nucleic acid cargo within but also displays a variety of biomolecules that may be modified to improve delivery performance. EVs can be produced in large quantities from primary red blood cells (RBCs) at relatively low costs. Leveraging these strengths, our group have worked with collaborators and industry partners to develop and validate an efficient method of loading nucleic acids into RBCEVs using the REGENT® platform. Importantly, we have successfully conjugated peptides and antibodies to therapeutically loaded RBCEVs for targeted delivery. We have employed these technologies to deliver RIG-I agonists as immunotherapy to suppress breast cancer and its metastasis to the lungs. We are also exploring the use of RBCEVs to deliver small interfering RNAs to alleviate cancer cachexia and antisense oligonucleotides to treat COVID-19, with encouraging data in cell and mouse models. The feasibility of loading these different nucleic acids that target different diseases highlights the versatility of the RBCEV platform and suggests its future development for diverse applications.
Bio: Dr. Le graduated from the National University of Singapore in 2005 with a bachelor’s degree in Life Sciences. She further received a Ph.D. degree in Computational and Systems Biology from the Singapore-Massachusetts Institute of Technology (MIT) Alliance under the guidance of Prof. Bing Lim at the Genome Institute of Singapore and Prof. Harvey Lodish at the Whitehead Institute for Biomedical Research. From 2010 to 2015, she took a postdoctoral training under Prof. Judy Lieberman at Boston Children’s Hospital and Harvard Medical School in the USA. From 2015 to 2019, she worked as an Assistant Professor at the Department of Biomedical Sciences at City University of Hong Kong (CityU). She became a tenure-tracked Assistant Professor at Department of Pharmacology, National University of Singapore, in 2019.
Dr. Le is well recognized for her contributions to the field of microRNAs (miRNAs), extracellular vesicles (EVs) and cancer biology. She was the first to identify a miRNA that regulates p53, an important tumor suppressor gene. This miRNA, miR-125b, was subsequently found to be a potent oncogenic miRNA in leukemia and many solid tumors. Dr. Le characterized the anti-apoptotic functions of miR-125b in zebrafish embryos and mammalian cells. She demonstrated that this tiny RNA is dispensable for normal development as it regulates the delicate balance between cell death and growth by repressing the p53 gene network. Furthermore, during her postdoctoral training, Dr. Le illustrated a novel mechanism of cancer crosstalk in which miRNAs secreted by metastatic breast cancer cells are delivered to non-metastatic cells via extracellular vesicles (EVs) and promote colonization of tumor cells in the lung. Recently, our group has established a new EV-based drug delivery platform with efficient and safe delivery of RNA drugs to cancer cells. With these original findings, Dr. Le’s articles have been cited over 2,000 times by researchers worldwide (link).
In addition to her interest in research, Dr. Le also has a passion in education. She has organized the translation of “Molecular Cell Biology”, an American biology textbook by Lodish et al., into Vietnamese. As the project coordinator for the last 10 years, she has brought together the American authors, Vietnamese scholars, publishers, sponsors and hundreds of backers, to translate the most advanced knowledge in biology and promote science education in Vietnam. The book has been warmly welcomed by scientists and biology students in the country (link). Dr. Le also co-organized the Hong Kong RNA club for education in RNA research (link) and the EV journal club at the Singapore Society for clinical, research and translation of EVs (SOCRATES).
Dr. Le was awarded several prestigious scholarships and fellowships during her studies such as the Lee Foundation study grant and the Singapore-MIT Alliance scholarship. She was one of the first three recipients of the L’Oréal Singapore for Women in Science National Fellowship broadcasted widely by the news in 2009 (link). During her training at Harvard Medical School, she was awarded the Jane Coffin Childs fellowship, a prestigious postdoctoral fellowship in the USA. She also won a number of competitive travel scholarships and poster awards at international conferences. As an independent investigator, she has won various competitive external grants in Hong Kong and Singapore.
Dr. Le is currently an associate editor of the Journal of Extracellular Vesicles (JEV) and a deputy editor of the Journal of Extracellular Biology (JEB). She is also a scientific co-founder and advisor of Carmine Therapeutics (link), a start-up company based on red blood cell EVs, based in Singapore and Boston. Carmine Therapeutics has raised more than 10M USD seed funding and recruited about 20 employees. It was considered one of the top 15 biotech start-up companies in 2020.