AVI Biopharma is a company that has been around for many years, but, with little success for the first 20. According to Xconomy Seattle, AVI has been in business since the 1980s but, as of July 2009, had never had a product approved by the US FDA. A series of organizational changes, including new sources of funding, a new CEO and new research facility in Seattle, one of North America's largest biotech hubs, were made in the year that followed, in an effort to give the company new life.
The AVI platform technology is a novel kind of RNA-based antisense therapeutic. Unlike most siRNA technologies, AVI products are designed to target both messenger RNA (mRNA) and precursor mRNA, the form that hasn't had the introns spliced out yet. The products designed AVI to target precursor mRNA are called Splice Switching Oligomers (SSOs). The SSO approach takes advantage of the fact that many genes contain codes for more than one protein, and at the mRNA processing stage, the splicing pattern determines the protein that is formed. SSOs are designed to manipulate splicing to form an alternative mRNA, by causing protein polymerase machinery in the cell to bypass certain target exons. This process, called exon-skipping may inhibit formation of an unwanted protein, or promote formation of a desirable alternate. Depending on the genetic cause of disease, it might also result in removal or repair of a mutation.
AVI also produces Translation Suppressing Oligomers (TSOs) that bind tightly to mRNA target strands and sterically block translational machinery. The oligomer structure of AVI antisense products is altered by the use of morpholine rings instead of ribose, as the sugar backbone, and replacement of phosphodiester bonds with phosphorodiamidate bonds, which alter the polymer backbone charges and the potential for ionization within a cell. These changes play a role in the efficacy and safety of the drug.
A treatment for Duchenne Muscular Dystrophy (DMD), using exon-skipping, was cited as the company's "Lead Program" by the AVI Biopharma website at the end of 2010. DMD is a genetic disease that affects children and is caused by mutations in the gene for dystrophin, a key protein in the formation of muscle fibers. Drug candidates have been made to direct RNA processing that skips certain exons (particularly exons 50 or 51) of the mRNA, resulting in shorter but still functional dystrophin proteins. In July 2010, the website predicted that approximately 85% of DMD patients could be treated with their technology.
As of October 2010, AVI Biopharma had several products in pre-clinical and clinical testing. Some of these are aimed at fighting other rare diseases; AVI has taken on some very ambitious projects for the US government, fighting infectious diseases like those caused by Ebola, Marburg and Dengue viruses. By taking advantage of Orphan Drug status for at least one of its DMD treatments, and the potential for this designation for other drugs in the pipeline, AVI might see approval for more than one new drug in the next decade.
Timmerman, L. 2009. AVI Biopharma Bolts from Portand to Seattle to Tap Biotech Talent. Xconomy Seattle, July 30, 2009. Accessed October 31, 2010 online at: http://www.xconomy.com/seattle/2009/07/30/avi-biopharma-moves-headquarters-from-portland-to-seattle-to-tap-biotech-talent-pool/.