Genteric is harnessing the body's ductal system to get genes into the gastrointestinal organs and on into the circulation, without directly confronting the circulatory system. The firm believes this direct route will improve transfection rates and reduce immune reactions, regardless of the sort of vector--and has been pitching gene-therapy companies on the concept. So far, they've been hard to convince, but Genteric is confident they will come to appreciate the benefits of its delivery method.

Ten years ago, researchers observed that injecting vascular endothelial growth factors or fibroblast frowth factors into animal models of ischemia stimulated the formation of new blood vessels. The discovery that, with a bit of prompting, the body's natural capacity for angiogenesis could be accelerated, has drawn more than a dozen drug firms and a handful of cardiovascular device companies into the search for a biological alternative that can aid or replace current cardiovascular interventions, or even delay the progression of heart disease.

The devices that are necessary for most gene therapy approaches put interventional device companies in a perfect position to profit from their biological discoveries. Boston Scientific Corp. is determined to be the leading light in the field, and last month it acquired gene therapy start-up CardioGene.

The new gene therapy start-ups are learning to live with the technology’s limitations--and even to exploit them. While systemic treatments have generally failed, largely because doctors couldn’t deliver high-enough and frequent-enough doses to overcome the relatively low transfection rates and short-term expression, new companies are targeting localized diseases, in vascular medicine, wound care and certain neurological conditions, in which treatment doesn’t require long-term expression and where direct delivery of genes maximizes the effective dose.