時間：2025-07-24(四) 10:30 am

講題：Polymeric lysosome-targeting chimeras (PolyTACs): extracellular targeted protein degradation without co-opting lysosome-targeting receptors

講者：Hung-Hsun (Ryan) Lu

服務單位：Department of Chemistry Center for Bioactive Delivery, Institute for Applied Life Science University of Massachusetts Amherst

地點：4樓創意講堂

主持人：孫亞賢 教授

摘要 :

Extracellular targeted protein degradation (eTPD) is an emerging modality for regulating
protein levels without genomic interruption. Current strategies typically co-opt lysosome-
targeting receptors (LTRs) that are ubiquitously present in most cells, providing a high
success rate of eTPD across cell types and tissues, but potentially suffering from on-
target, off-site effects. Yet, exploring LTR-independent access to eTPD would introduce
an arguably nimble molecular design paradigm that opens up new opportunities in many
diseases with no suitable LTRs. Here, we report polymeric lysosome-targeting chimeras
(PolyTACs), a polymer-antibody conjugate based platform for the targeted degradation
of membrane-bound and soluble proteins without the need for involving LTRs.
Mechanistic investigations suggest a non-classical uptake pathway that is attributed to
the membrane stress caused by the multivalent interactions between the PolyTACs and
the overexpressed functionalities on the cell surface. The scaffold offers a distinct dual-
targeting mechanism involving antibody-mediated target recognition and polymer-
mediated biomarker identification. The design and fabrication simplicity, non-reliance on
LTRs, and tissue-targeting capabilities open up new avenues for eTPD in many
disease-specific applications.

學歷 :

Education
2020-present Ph.D. Candidate (NIH-UMass Biotechnology Training Program Fellowship)
Department of Chemistry, University of Massachusetts-Amherst
(Advisor: Prof. Dr. Sankaran Thayumanavan)

2014-2016 Master of Science

Department of Chemistry, National Tsing Hua University
(Advisor: Prof. Dr. Chi-How Peng)

2010-2014 Bachelor of Science

Department of Biomedical Engineering and Environmental Science, National Tsing Hua University
02/2024-10/2024 Credential of Readiness (CORe) – Certificate Courses: Business Analytics, Economics for Managers,

and Financial Accounting
Harvard Business School Online

Research Interests
➢ Controlled polymerization techniques, including atom transfer radical polymerization (ATRP), reversible addition–
fragmentation chain transfer (RAFT), and ring-opening metathesis polymerization (ROMP)
➢ Polymeric systems for targeted delivery of therapeutic agents, including small molecules, genes, and proteins
➢ Antibody–polymer conjugates for targeted protein degradation and anticancer molecule delivery
➢ Functional polymers for processing advanced electronic materials

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