Qiuming Chu

1) Proposed, led the development and execution of a small molecule therapy for Transthyretin amyloidosis (ATTR); directly targeting the root cause of the disease, unlike the current drug, Tafamidis, on the market; confirmed the hypothesis; organized/led the team/project including members from various groups such as discovery, translation, development, business, preclinic, plus academic lab and CROs; and identified a series of potential chemical structures for the targeted protein through putting extra efforts and digging deeper with my encouragement. Confirming the hypothesis has already turned the impossible into possible. There is an even larger patient population for the new potential drug than the current blockbuster. 2) Proposed oral siRNA/milk exosomes (mExo) therapy for Wilson disease (WD); developed a practical method for isolating mExo for potential large-scale production; created a technique with significantly higher siRNA loading than reported in literature; achieved positive uptake and gene knockdown results in vitro. The loading approach is unique compared to existing literature. siRNA/mExo delivery could enable oral administration for siRNA, ASO or mRNA, and expand applications for other diseases. 3) Proposed a sequential therapy to target specific cells for CNS diseases [Alzheimer’s disease (AD), Parkinson's disease (PD), Multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS)…]; developed an in vitro simple cellular model and proved the hypothesis; also serving as a high-throughput screening tool for identifying potential therapeutic candidates. No similar reports found in literature. The sequential therapy could revolutionize the disease treatment strategies by significantly enhancing clinical efficacy. 4) Proposed a bispecific antibody for the treatment of CNS diseases and collaborated with colleagues to establish assays. 5) Involved in lipid peroxidation inhibition in CNS diseases, contributing to novel therapeutic approaches.

1) Involved in small molecular therapy for Cystic Fibrosis (CF) disease from the beginning, pre-M0, to M0, M1, PC and M2 as of initial few people to start the project. We also got funding from CF foundation. 2) Involved in small molecular therapy for Alpha-1 antitrypsin (A1AT) deficiency (A1AT).

1) Developed mouse models for evaluating RNAi therapy to evaluate ASO from Ionis, which supported the late co-development for our company with Alnylam for the first FDA-approved siRNA therapeutic drug. 2) Proposed and executed IGF-1 therapy for diabetic peripheral neuropathy, leading to a publication 3) Proposed and conducted research on intrathymic immune tolerance for gene therapy, resulting in a publication and a patent application. 4) Contributed to various projects on rare diseases, resulting in publications.

1) Proposed and executed research of enhancing immune tolerance to transgene products by siRNA for gene therapy, leading to the first siRNA paper from our company. 2) Proposed solutions and executed research on gene delivery for cystic fibrosis (CF), after investigating and identifying reasons for the failure of non-viral gene delivery in clinical trials. This work resulted in one publication and one patent on the underlying issues, and another publication on enhancing gene delivery using Adeno-associated virus (AAV) vectors. Additionally, identified a peptide with potential for non-viral delivery to airway cells for the disease. 3) Developed gene delivery methods targeting the liver and muscle for Rare diseases (e.g., Fabry and Gaucher). This involved learning high-volume injection and tibialis anterior muscle injection techniques in mice from academic labs, then establishing high-volume injection in rats in-house, and further collaborating with a Harvard clinical radiologist to develop catheter-based procedures for liver gene delivery in rabbits and non-human primates, resulting in publications.

Supported clinical trials for non-viral gene therapy using aerosol delivery of lipid/pDNA complexes, contributing to advancements in gene therapy research for cystic fibrosis (CF) disease.