February 21, 2007
Despite some early setbacks, scientists continue to make steady progress with gene therapy. The advances have brought new bioengineering needs, including a wish for a nonviral gene-delivery vector, such as plasmid DNA, that is as efficient as or better than today’s viral systems but without the associated safety concerns. To date, most of the research has focused on hammering out a better nonviral vector. Largely ignored in the equation is the target of the vector - the extracellular matrix, or ECM, the gateway into the cell. As many have noted, the chemical and mechanical landscape of ECMs vary among tissues, strongly indicating that even the most elegantly designed vector won’t yield optimum results unless it is well suited to exploit the specific molecular terrain of its target.
In the January issue of the journal Nano Letters, NIDCR grantees and colleagues add fuel to this argument in studies with cultured pre-osteoblasts, or bone-producing cells, adherent to synthetic ECM adhesion ligands. They found that the levels of gene transfer and expression increased with the density of the adhesion ligands but decreased with the spacing of the ligands, likely from changes in the growth rate of the cells. The scientists stated their results show for the first time in a synthetic material that the number and nanoscale distribution of cell adhesion molecules can serve as a “control point” to regulate nonviral gene delivery. They anticipate that these results can be reproduced in other cell types and cell adhesion-promoting biomaterials and ultimately help to improve the quality of various gene-based therapies.