A versatile new platform technology could enable doctors to release DNA locally in the body for a variety of therapeutic applications.
Using a layer-by-layer fabrication process, Chemical and Biological Engineering Associate Professor David Lynn (left, pictured with PhD student Shane Beckler), can coat complex medical devices, such as vascular stents, with alternating nanoscale polymer and DNA layers. When doctors insert these devices into the body, the coatings will break down and control how slowly or rapidly DNA is delivered. “The idea is local therapy,” says Lynn. “You can avoid some of the problems associated with administering something systemically.”
DNA needs a delivery agent to help it cross cell membranes and enable the cells to process it effectively. Positively charged, or cationic, polymers are a popular method for delivering DNA. Lynn and his students make and synthesize cationic polymers that will assemble with DNA in solution to form nanoparticles or on surfaces to form films. They are layering their cationic polymers alternately with DNA to form multilayered thin films on medical devices, including stents, balloon catheters or microneedle arrays. “Layering allows you to control the amount of DNA or drug that’s incorporated, simply by the number of layers that you add, so that you can control the dose,” says Lynn.
Initially, he and his students focused on building stable polymer films that would “fall apart” in the body and release DNA. Now, they are taking this platform and making it useful for controlled, timed DNA delivery. With collaborators at UW-Madison and elsewhere, Lynn and his students are expanding their basic understanding into in vivo studies in animals. “We’re out of the tool-building phase and entering the phase where we can try some interesting things in a potential therapeutic context,” says Lynn.
Ultimately, Lynn, whose funding for the research comes from the National Institutes for Health, hopes use to this approach to coat devices with multiple different layers of multiple different drugs. “Then, you have a potentially sophisticated way to release multiple drugs in a controlled way over time, which is something that is difficult to do using conventional approaches,” he says.