Non-viral gene therapy to accelerate cancer research

The non-inserted, bioinspired, gene delivery method developed by researchers at RMIT University has proven effective in laboratory testing and is safer than standard viral approaches.

Widely regarded as the next frontier for cancer research, gene therapy involves introducing new genes into a patient's cells to replace the missing or failing genes that cause the disease.

Since cells are not designed to naturally support genes or any foreign DNA material, the main challenge of gene therapy is to get the therapeutic genes into the cells.

Research has focused on the use of viral delivery systems to penetrate cells. However, the risks associated with introducing a virus into the body have slowed progress from one laboratory to the other and only three virus-based treatments have already been approved by the FDA.

Although they are safer and relatively inexpensive, less than 0.25% of gene therapy research has focused on non-viral methods because of varying outcomes.

Lead researcher Dr. Ravi Shukla said reducing gaps in appropriate non-viral methods would be a key step in moving gene therapies out of laboratories and clinics.

"An effective non-viral method would be safer for patients and could significantly reduce the time and cost of bringing new treatments to market," he said.

"We have now successfully tested a non-viral alternative that could enable us to avoid the risks associated with viral methods and help unlock the full potential of gene therapy."

Shukla and his team have developed the new non-viral method using extremely versatile and super-porous nanomaterials that can be used to store, separate, release or protect almost all biomolecules.

The research is funded by the Commonwealth Scientific and Industrial Research Organization (CSIRO), which has developed a technology to manufacture MOF quantities on an industrial scale.

Mainly used for industrial or chemical purposes, the biological applications of MOFs are gaining ground and these latest findings show that they have excellent potential in non-viral gene therapy.

The researchers used a subtype of MOF known for its biocompatible and biodegradable properties to transport DNA in a cell.

The MOF-based delivery method has proven effective in prostate cancer cells and paves the way for the treatment of lung and breast cancer as well as other genetic diseases.

Ph.D. Researcher Arpita Poddar, who worked with Shukla on the discovery, said these discoveries were the first step towards opening a line of research so far neglected.

"Now that we have a proof of concept, we can study other applications, including transgenomics, implants and even crop improvement," she said.

The document, Encapsulation, visualization and gene expression with zeolitic imidazolate biomimetically mineralized Framework-8 (ZIF-8), is published in Small.