# Continuous Production of Viral Vectors using membraneless Perfusion Culture of Host Cells

> **NIH FDA R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2022 · $600,000

## Abstract

Project Summary Abstract
Continuous Bioproduction of Viral Vectors via High Cell Density, Membrane-less Perfusion Culture
In this project, we propose to intensify the viral vector production process by the membrane-less perfusion
bioreactor system, which was developed by our team at MIT. Based on the inertial microfluidics and fully
validated in CHO cell cultivation, this system has many critical advantages over existing perfusion bioreactors,
including high product recovery and avoiding membrane fouling, continuous removal of dead cells, cell debris,
and cell aggregates, and easy maintenance and automation. As a result, our bioreactors can maintain high cell
density reliably even when the cell viability and culture conditions change significantly, ideally suited for
controlling viral vector production processes. Teaming with experts in HEK293 and Sf9 based production
systems, we will implement long-term, high cell density cultures of host cells and explore and validate several
innovative vector production platforms that provide more accurate control over fresh cell growth, transfection,
incubation/production, and recovery of the products. Inertial microfluidic cell manipulation processes allow
many novel controls over host cells in bioreactors, including selective separation of transfected from
untransfected host cells. Finally, a continuous bioprocessing system will be optimized to maximize the quantity
and quality of the finished viral vector products. For this, we will employ novel microfluidic electrokinetic
separation of empty from filled viral capsid, which can provide near real-time determination of the quality of the
product. In contrast to fed-batch or batch cultures, continuous monitoring of vector quality and quantity enables
rapid adjustment of the culture protocols to restore/maintain optimal conditions for vector production over an
extended period. This project is expected to have a broader impact on the bioproduction of viral vectors, but
especially on rare and ultra-rare diseases where low disease prevalence requires relatively small production
volumes. Such diseases do not justify the biopharmaceutical industry’s large investment needed for vector
manufacturing.

## Key facts

- **NIH application ID:** 10486077
- **Project number:** 5R01FD007480-02
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** JONGYOON HAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2022
- **Award amount:** $600,000
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10486077

## Citation

> US National Institutes of Health, RePORTER application 10486077, Continuous Production of Viral Vectors using membraneless Perfusion Culture of Host Cells (5R01FD007480-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10486077. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*