09/03/2025
By Danielle Fretwell

The Francis College of Engineering, Department of Chemical Engineering, invites you to attend a Doctoral Dissertation defense by George Liang on: "Exploring the Impact of N-Linked Glycans on rAAV Transduction and Stability"

Candidate Name: George Liang
Degree: Doctoral
Defense Date: Wednesday, September 10, 2025
Time: 10 a.m.-Noon
Location: University Crossing, Room 490

Committee:
Advisor: Seongkyu Yoon, PhD, Chemical Engineering, University of Massachusetts Lowell

Committee Members*
1. Bryan Black, PhD, Biomedical Engineering, University of Massachusetts Lowell
2. David McNally, PhD, Chemical Engineering, University of Massachusetts Lowell
3. Garry Handelman, PhD, Biomedical & Nutritional Sciences, University of Massachusetts Lowell
4. Sanjeev Manohar, PhD, Chemical Engineering, University of Massachusetts Lowell
5. Sha Sha, PhD, Ultragenyx

Abstract:
Recombinant adeno-associated virus (rAAV) vectors are widely used in gene therapy due to their low immunogenicity and effective gene delivery. However, pre-existing immunity and variability in vector performance remain significant challenges. Among the critical quality attributes (CQAs) of rAAVs, capsid tropism plays a key role in determining vector stability and transduction efficiency. While various
post-translational modifications (PTMs)—including phosphorylation, ubiquitination, SUMOylation, acetylation, and deamidation—are known to impact capsid function, glycosylation has received limited attention due to its low abundance in rAAV capsids.
In this study, we investigated the role of N-linked glycosylation in modulating rAAV transduction and stability. Using a combination of endoglycosidase and exoglycosidase treatments on intact rAAV serotypes, we assessed the functional consequences of altering glycan profiles. Our findings indicate that high mannose-type glycans, although present in low levels, may contribute to protecting capsid regions from deamidation, thereby preserving transduction efficiency. In contrast to other biologics such as monoclonal antibodies, N-linked glycosylation had minimal effect on rAAV aggregation or physical stability.
These results highlight a subtle yet potentially important role of glycosylation in rAAV biology and suggest that glycoengineering approaches—such as plasmid-based modulation of glycan heterogeneity—may offer new strategies to enhance vector performance for clinical gene therapy applications.