Hassan Fakih
Postdoctoral fellow UMASS Chan Medical School
Hassan is a Postdoctoral Associate in the lab of Prof. Anastasia Khvorova at the RNA Therapeutics Institute at UMass Chan Medical School. His research focuses on improving the extra-hepatic delivery of siRNA therapeutics using self-assembled nucleic acid particles and lipophilic conjugation. Hassan is particularly interested in developing therapeutics for the treatment of muscle diseases, oncology and CNS disorders.
Building on his premedical chemistry B.Sc. (American University of Beirut, 2016), Hassan earned a Ph.D. in chemistry at McGill University working in the Sleiman lab (2016-2021). His doctoral research focused on developing DNA nanocarriers for nucleic acid therapeutics. He designed and tested DNA-based nanocarriers optimized for faster clinical translation, prioritizing improved cost-effectiveness, biocompatibility, specificity, and stability. This work led to the development of sequence-controlled nucleic acid-polymer conjugates that self-assemble into spherical nucleic acids (SNAs) with stimuli-responsive activation. Additionally, he worked on chemically modified SNAs demonstrating promising efficacy without transfection agents. Following his successful Ph.D., Hassan joined the Khvorova lab to further advance translational research in the field of oligonucleotide therapeutics.
Seminars
This workshop examines the mechanistic and translational determinants of intrathecal siRNA delivery in CNS disorders. While achieving broad exposure from CSF is increasingly feasible, translating this into effective and uniform gene silencing across brain region, particularly in deep structures, remains a central challenge. Using non-human primate datasets, crossspecies comparisons, and exposure–response frameworks, this session will explore whether emerging delivery strategies can overcome anatomical and pharmacokinetic barriers in CNS tissues.
Highlights Include:
- Dissecting the distribution of siRNA from CSF into cortical versus deep brain structures, including physical and molecular factors influencing penetration and spatial heterogeneity
- Distinguishing gross tissue exposure from functional intracellular uptake across CNS regions
- Exploring how delivery efficiency influences tissue retention, clearance dynamics, and durability of knockdown
- Discussion on acute tolerability signals, concentrationdependent toxicity, and whether improved efficiency can shift effective dose ceilings
- Evaluating whether current and emerging intrathecal siRNA strategies are sufficient for diseases affecting subcortical structures
