Graduate Student Seminar Series – Fanglin Gong

Graduate Student Seminar Series
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Location: MS2158 – 1 King’s College Circle
Presentation Title: Lipid nanoparticles optimized for large RNA cargo enhance genome editing in mouse liver, lung and brain
Abstract: Non-viral delivery of large gene editors remains a major barrier to unlocking the therapeutic potential of genome editing. Although lipid nanoparticles (LNPs) are clinically validated for RNA delivery, their efficacy often declines when encapsulating larger mRNA transcripts necessary for genome editing. In this work, we present a large-cargo-informed lipid discovery strategy that incorporates mRNA size into the rational design and screening of LNPs. By synthesizing a library of over 300 unique ionizable lipid candidates and evaluating their performance using multi-kilobase reporter mRNAs, we identified a class of large-cargo-optimized lipids (LC-lipids). The lead ionizable lipid, LC-1, enabled improved Cas9 gene knockout and adenine base editing across multiple tissue types and administration routes, including the liver (intravenous), brain (intrathecal), and lung (intratracheal), consistently outperforming benchmark LNPs using LP-01 and ALC-0315 as the ionizable lipid.
Supervisor Name: Dr. Bowen Li
Year of Study: 4
Program of Study: PhD
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