Lincoln, NE - Around the world, more than 3,000 biotechnology and pharmaceutical companies use transplanted genes to make biological products in living cell factories, as well as for gene therapy and genetic immunization research. A significant problem for the industry as a whole is that the foreign genes which they use (called transgenes) are often inactivated soon after they are inserted into their host cells, making them useless.
NTC, which has made great strides at improving gene tools (vectors) in the past, has now been awarded a $146,641 Small Business Innovation Research (SBIR) Phase I grant for pilot studies aimed at reducing or eliminating the gene silencing phenomenon. The grant award was funded by the National Institute of General Medical Sciences, of the National Institutes of Health (NIH).
“Gene silencing has been a major stumbling block for gene therapy, and for the biologics industry as a whole,” said Clague Hodgson, NTC’s president, adding that, “The phenomenon has multiple causes and is generally related to the host cell’s defense against invading pathogens, part of the innate immune system, which is also the first line of defense against viral and bacterial infections.”
“Avoiding such elaborate host defense systems in order to reprogram the genetics of the host cell requires some careful engineering maneuvers, equivalent to planting a Trojan horse,” according to Dr. Jim Williams, the Principal Investigator on the grant. To accomplish their goals, NTC researchers will test several tricks designed to overcome the silencing phenomenon.
First, they will alter certain essential DNA sequences in the vectors that ‘look foreign’ to the cell, reducing chances that they will be earmarked for silencing.
Second, they will eliminate antibiotic resistance genes, which are a specific target for silencing, and are a worry to the FDA as well. That goal has recently been accomplished by NTC, according to Williams.
Finally, they will redesign the vectors, so that gene activity is maintained at a high level in the DNA sequences flanking the critical transgenes. This is intended to fool the cell into behaving as though the transgene is a normal, active component of the cell, as opposed to appearing to be inactive ‘junk DNA’, which would otherwise be earmarked for silencing.
If successful, the research can then be applied in most areas of the biotechnology industry, including for production of recombinant proteins, peptides and hormones, as well as for gene therapy and genetic immunization (DNA vaccines).
Phase I SBIR grants are intended to support limited proof-of-concept studies. If Phase I grant milestones are successfully met, a larger Phase II grant may be funded, which is expected to lead to commercial products and processes.
NTC has a history of successful commercialization of its discoveries, according to Hodgson. “We are working in the trenches every day, and we can move discoveries from the lab bench, to the process, to the product in one shop,” he said, adding, “It’s the beauty of being a small company, able to turn on a dime.”
The current award is the seventh SBIR award made to NTC since 1997.