Sheng Zhang

• Built an in-house GalNAc siRNA oligonucleotide analysis platform for Takeda's San Diego site through instrumentation setup, method development, technology transfer (Japan to the U.S.), and method optimization (hands-on) • Characterized, formulated, and evaluated the formulations of oligonucleotides using the methods I developed, including moisture content through Karl Fischer, extinction coefficient through UV-vis, osmolality, viscosity, turbidity, sub-vis particles, auto-titration, Tm, and stability through ion-pairing HPLC • Developed a nephelometry-based method for rapid screening of small molecule solubility • As the analytical-pharmaceutical research representative of the project, I drove the lead candidate selection, developability assessment, formulation evaluation, and IND preparation of oligonucleotides by data-driven communication with senior staff from R&D, analytical, process chemistry, and formulation departments in Boston, San Diego, and Japan • Led an oligonucleotide working group (with Directors and Scientists) to foster collaboration and tech transfer between San Diego and Boston sites • Presented my work on building an oligonucleotide analysis platform on behalf of the San Diego site at the PharmSci poster session in Boston.

• Developed analytical methods for mRNA drug substance and formulated mRNA-LNP vaccine drug product (5' cap and polyA sample prep and LC-MS analysis, size through DLS, purity through ion-paring HPLC/UPLC and CE, concentration through UV-vis) • Analyzed formulated antibody drug products (enzymatic treatment, peptide mapping, intact mass, DSC, DLS, stability, PS80, appearance) to support preclinical activities • Authored characterization reports for antibody and mRNA-LNP by reviewing data from myself, research associates, CROs, and CTLs • Authored and reviewed SOPs, IND documents, QC reports, method qualification reports, and IQ/OQ documents per FDA and USP guidelines • Led quality control and method qualification of antibody and mRNA-LNP (in-process, release, in-use syringe, and stability) while supervising 4 research associates • Transferred methods to R&D, nanoformulation, GMP manufacturing, QC microbiology, facility, and QA teams

Research advisor: Distinguished Professor James S. Nowick • Generated disulfide-bond-stabilized non-covalent Amyloid-beta peptide dimers with beta-sheet structures by molecular cloning (restriction enzyme, PCR), E. coli expression, and purification (prep-LC and IEX) • Performed peptide bioconjugation, solid-phase peptide synthesis, and characterization (HPLC, MALDI-MS, SEC-MS, ion-mobility MS, LC-MS, fluorescence assay, DLS, CD, SDS-PAGE, NMR) • Developed aggregation-prone Amyloid-beta peptide expression, purification, and conjugation methods that increased the yield, cut down production time, reduced costs, and obtained higher purities compared to the literature-reported method • Published a protocol on the structure-based drug design of a cyclic peptide inhibitor for the COVID-19 main protease using computational molecular modeling

Research advisor: Professor Qiao-Hong Chen • Solution-phase synthesized, purified (prep-TLC; column chromatography), and analyzed (NMR) small molecules (natural products derivatives) • Studied structure-activity relationship through structural modification and mammalian cell-based potency assays

• Performed molecular biology research, including gene editing, E. coli protein expression, protein purification (IMAC), and analysis (gel shift assay)

Research advisor: Distinguished Professor James S. Nowick