Cover image for Highlights in Chemical Biology

Highlights in Chemical Biology

Chemical biology news from across RSC Publishing.



The viral production line


30 November 2007

Not all viruses are bad news...

"Viruses survive at body temperature for only a few hours so new ways of producing large amounts of virus are in demand"

Martin Yarmush and colleagues at the Massachusetts General Hospital in Boston, US, have designed a microfluidic bioreactor that can generate a continuous stream of freshly produced retrovirus ready for immediate use. 

Having evolved over millions of years, viruses are nature's specialised gene delivery vehicles. Retroviruses in particular are able to introduce genetic material into target cell DNA, providing long-term gene expression. It is this ability that makes them ideal for use in gene therapy; by introducing genes modified to have a therapeutic effect they can be used to treat or even cure disease. However, their use in medicine is hindered because the viruses survive at body temperature for only a few hours so new ways of producing large amounts of virus are in demand. 

Schematic of experimental setup for the incorporation of low temperature preservation for virus sample collection with the microdevices

Packaging cells held in channels in a bioreactor can make a continual stream of retrovirus

In Yarmush's bioreactor, virus is produced by so-called packaging cells held in the channels of the device. When the researchers compared the bioreactor's virus output with conventional, static, tissue culture methods, they found a 1.4- to 3.7-fold increase over 5 days. This higher output was obtained only when the virus was exposed immediately to low temperatures to prevent its rapid degradation. 

John Yin, an expert in biomedical engineering at the University of Wisconsin-Madison, US, explained that the work demonstrates that microfluidic systems can be used to quantitatively characterise virus production and control culture conditions. 'It offers potential automation of an otherwise labour-intensive process,' he said.

By collecting and flowing virus supernatant (fluid) over target cells, the team confirmed that the bioreactor could be used to infect target cells with virus. Halong Vu, a member of the Boston team, described it as a first step toward developing more sophisticated devices to study viral targeting and infection dynamics for viruses in flowing liquids, such as the bloodstream, for gene therapy applications.
 
Janet Crombie

Link to journal article

A microfluidic bioreactor for increased active retrovirus output
Halong N. Vu, Yawen Li, Monica Casali, Daniel Irimia, Zaki Megeed and Martin L. Yarmush, Lab Chip, 2008, 8, 75
DOI: 10.1039/b711577f

Also of interest

A high-throughput microfluidic real-time gene expression living cell array
Kevin R. King, Sihong Wang, Daniel Irimia, Arul Jayaraman, Mehmet Toner and Martin L. Yarmush, Lab Chip, 2007, 7, 77
DOI: 10.1039/b612516f

Microfabrication-based modulation of embryonic stem cell differentiation
Jaesung Park, Cheul H. Cho, Natesh Parashurama, Yawen Li, François Berthiaume, Mehmet Toner, Arno W. Tilles and Martin L. Yarmush, Lab Chip, 2007, 7, 1018
DOI: 10.1039/b704739h

Instant insight: Mutants make more

Andreas Kirschning explains how genetically modified microbes offer a short-cut to valuable derivatives of natural products