Protein protection for genetic delivery

Microcapsules offer a novel route for DNA-based drugs.

Medicines based on DNA, whether gene therapy or DNA vaccines, offer new approaches to treating a number of chronic diseases. One of the hurdles that still needs to be overcome, however, is how to deliver the DNA to the patient in a manner that prevents it from degrading during its journey and allows it to penetrate the target cell.

Researchers at Louisiana Tech University, Ruston, US, and the Max Planck Institute of Colloids and Interfaces, Potsdam, Germany, claim to have developed a possible solution, involving DNA encased in a specially designed microcapsule

The microcapsule is built up from alternating layers of two types of biocompatible polymer: poly[?-glucuronic acid- N-acetyl-?-galactosamine-6-sulfate] (PG); and poly(-l-arginine) (PA). Four layers of PA and PG, each 5 nm thick, self-assemble around a spherical MnCO ₃ particle with DNA molecules on its surface.

The MnCO ₃ particle is then dissolved with de-aerated hydrochloric acid to leave biocompatible microcapsules in which the DNA molecules float freely. By studying the circular dichroism spectra of the DNA, the researchers showed that the molecules retained their double-helix structure through the capsule formation process. The DNA molecules are naturally released from the microcapsules in slightly acidic environments (pH < 3).

In order to study the formation process, the researchers only created the microcapsules using MnCO ₃ particles which were 4mm in diameter.

However, they claim that smaller capsules (200-300nm) could also be created for targeted delivery of DNA to living cells.

Jon Evans