Study promises safer, more effective gene therapy

Washington, June 26 : The major drawback of gene therapy was the risks associated with using viruses as vectors to deliver healthy genes, but a new University of Georgia study has found a safe and efficient gene delivery method that doesn't involve viruses.

Yan Geng, assistant professor of chemistry and her colleagues in the UGA Franklin College of Arts and Sciences have developed a novel synthetic gene vector that packages DNA into well-defined nanostructures enabling it to efficiently deliver genes without triggering immune responses.

Primarily carried out by doctoral student Jennifer Haley, the study may also have implications for cancer treatment and vaccine development.

"We've developed a very versatile approach to creating synthetic gene delivery vectors. Our approach is relatively simple - using simple chemical reactions to create a new class of packaging molecules that wrap up genes on their own - and has the potential to be very useful in real-world, clinical applications," said Geng.

In gene therapy, abnormal, disease-causing genes are replaced with normal genes, by using genetically modified viruses. Geng said that the viruses do a remarkable job of inserting the new genes into hosts, but they're inherently dangerous. So while the use of viruses as gene delivery vectors has been efficient, it also has led to unexpected and tragic complications, some of which were fatal.

However, he said that synthetic vectors, which use synthetic molecules to package genes, are generally safer than viral vectors. But, they're not as efficient.

"In nature, viruses are precisely self-assembled by their coating proteins and genome. We have to learn from nature and engineer a safer yet efficient gene delivery system for medical use," said Geng.

While synthetically packaging long strands of DNA into compact, small structures has long been a challenge, the researchers have developed a unique combinative self-assembly method that allows them to control precisely the size and shape of the vector.

They synthesized small peptides - which are short chains of amino acids - that bind to genes and emulate natural proteins to minimize potential immune reactions. The researchers then attach the small peptides onto a biocompatible polymer scaffold to create a clustered effect. The clustered peptides of the combined molecule will automatically assemble with DNA, while the polymer wraps around the assembly, creating a protective shell.

It was found that the assembly process is extremely sensitive to the clustered arrangement of the gene-binding peptides. To change the shape and size of the vectors, the researchers simply change the attachment density of the peptides on the polymer scaffold, resulting in shapes that vary from spherical to donut shaped to long filaments.

"These gene vectors also can be further conjugated with targeting molecules, which will allow us to deliver the right genes to the right spot in our body," added Geng.

The study appears in the latest issue of the journal Molecular BioSystems.

ANI