New discoveries accelerate progress towards affordable gene therapy

Researchers at RMIT University used enhanced metal-organic structures (MOFs) with a phytochemical coating of green tea to target human prostate cancer cells for the first time.

The new method of delivering the gene capture tool directly into target cells is a big step towards a more effective, safer and cheaper gene therapy with treatment potential for more genetic diseases.

Lead researcher, associate professor Ravi Shukla, said MOFs, which are versatile and biocompatible nanomaterials, are a viable alternative to existing viral methods for providing the CRISPR / Cas9 gene editing tool.

“MOFs have the ability to carry larger genetic loads and, as a non-viral option, have the added benefit of being a safer outlook for patients than viral alternatives,” he said.

Awarded the 2020 Nobel Prize in Chemistry, CRISPR / Cas9, it is widely recognized as a breakthrough in gene editing for its ability to remove and replace defective DNA, however the biggest challenge remains effective delivery to cells.

There are currently only 13 approved methods being tested globally and all rely on viral therapies, an extremely expensive approach with associated health risks.

RMIT had collaborated with CSIRO who had previously developed a technology to transport and protect biomolecules with MOF.

CSIRO research team lead, Dr Cara Doherty, said CSIRO has also developed technologies to produce industrial-scale quantities of various MOFs, with the potential to significantly reduce the cost of market introduction.

“We are thrilled to find a new way these materials can address complex biological issues, including targeting specific medicinal purposes such as gene therapy,” he said.

Cells are not designed to naturally absorb foreign genes or DNA material, and the risks associated with introducing a virus into the body have slowed the progress of research into viral methods.

To further enhance the MOF’s ability to enter the host cell, it has been coated with a phytochemical found in green tea called epigallocatechin-gallate (EGCG), known for its antioxidant and anticancer properties.

Co-author Arpita Poddar said EGCG worked by binding to the surface of the MOF, helping it enter the host cell.

“We found an increase in cellular uptake of more than 23% for EGCG-coated MOFs compared to uncoated ones,” he said.

The latest findings build on previous work by the team that developed a proof of concept for the delivery model late last year.

Next, they will work to further test this technology for its application in targeting several other disease-causing genes.

The article, “ZIF-C for Targeted RNA Interference and CRISPR / Cas9 Based Gene Editing in Prostate Cancer”, is published in ChemComm.