Enabling Technologies for Biomanufacturing Extracellular Vesicle-Based Therapeutics

Friday, October 25, 2024

4:30 PM – 5:00 PM EST

Location: Room 338

Invited Speaker(s)

Jamey D. Young, PhD (he/him/his)

Professor
Vanderbilt University, Tennessee, United States

Co-Author(s)

JW

John Wilson

Associate Professor
Vanderbilt University
Nashville, Tennessee, United States
EL

Ethan S. Lippmann, PhD

Associate Professor, Department of Chemical and Biomolecular Engineering
Vanderbilt University
Nashville, Tennessee, United States
AW

Alissa M. Weaver, M.D., Ph.D.

Professor
Vanderbilt University, United States
YJ

Youn Jae Jung, Ph.D.

Postdoctoral Scholar
Vanderbilt University, United States
RM

Rachel Moen

Graduate Student
Vanderbilt University, United States
HP

Hayden Pagendarm

PhD Candidate
Vanderbilt University
Nashville, Tennessee, United States

Introduction: There is growing interest in large-scale production of extracellular vesicles (EVs) due to their potential use as carriers of drugs or other biomolecules to diverse cellular targets. Despite the excitement generated by several early-stage EV biotech companies, the technology to mass-produce purified EVs with tunable and well-defined properties is still in its infancy. Our long-term goal is to develop technologies for scalable manufacturing of “designer EVs” that are engineered for efficient packaging and delivery of desired cargo molecules and can be produced from virtually any cell type.

Materials and

Methods: First, we plan to identify genes that can be engineered in mamalian production hosts to control EV loading and intracellular delivery of small RNAs to recipient cells. Second, we will develop a scalable workflow for producing EVs from differentiated human induced pluripotent stem cells (iPSCs), which provide a stable source of tissue-specific EV producer cells.

Results, Conclusions, and Discussions: We have identified genes that boost miRNA sorting into EVs when overexpressed in mammalian production hosts. We have also developed a 3D hydrogel matrix that can be used to encapsulate iPSCs in microspheres prior to growth and differentiation in stirred vessels, an approach that can be readily scaled-up to large culture volumes. EVs from 2D adherent and 3D hydrogel-based cultures are comparable in size distribution and structure, but 3D cultures provide substantial increases in EV volumetric productivity.

Acknowledgements (Optional): Funding support for this research was provided by NSF (Awards MCB-2036809 and CBET-2328276).