RNA Interference (RNAi) Technology: Cutting-Edge Technology for Immuno-Oncology

(DGIwire) – Sometimes a significant advancement in medicine results from the application of a proven technology in a novel area. In the field of immuno-oncology, as recently reported in Genetic Engineering & Biotechnology News (GEN), a potential path forward could be the use of self-delivering RNAi compounds to treat cancer.

RNAi is a naturally occurring process by which a particular “messenger RNA” can be destroyed before it is translated into protein. Since the overexpression of certain proteins plays a role in many disease conditions, the ability to inhibit gene expression with RNAi provides a potentially powerful tool to treat a range of human diseases. Various researchers are focusing on adapting RNAi technology for a new class of therapeutics that has the potential to address various conditions.

For example, RXi Pharmaceuticals is a clinical-stage RNAi company developing therapeutics based on its proprietary self-delivering RNAi (sd-rxRNA) platform. RXI-109, an sd-rxRNA compound, is currently being evaluated in clinical trials for dermatological and ophthalmological conditions. Earlier this year, RXi acquired MirImmune Inc., a privately held biopharmaceutical company focused on the development of new-generation immunotherapies for cancer. This acquisition expanded the RXi’s pipeline to include cell-based immuno-oncology.

“Scientists at RXi have designed chemically modified RNAi compounds with improved drug-like properties that are potent, stable and specific. These proprietary compounds have built-in delivery properties and therefore do not require a delivery vehicle. This allows for local therapeutic application in areas that include, but are not limited to, the skin, eye and the ex vivo treatment of cells,” explains Geert Cauwenbergh, President and CEO of RXi Pharmaceuticals. “For example, in the area of immuno-oncology using the adoptive cell transfer (ACT) approach, T-cells are isolated from patients and treated to silence immune suppression checkpoints. After which, the cells are reintroduced into the patient to target cancer. Therapeutic sd-rxRNA compounds are currently being developed at RXi for the treatment of solid and blood cancers.”

RNAi compounds may have the potential to silence any human gene, including those that are undruggable, reports GEN. To achieve this potential, however, RNAi compounds may need to have improved drug-like properties: potency, stability and specificity. One way to develop such properties is through chemical modifications.

The proprietary combination of chemical modifications that results in spontaneous cellular uptake of sd-rxRNA without the need for a delivery vehicle was discovered through systematic medicinal chemistry screening at RXi. sd-rxRNAs are hybrid oligonucleotide compounds that RXi believes combine the beneficial properties of both conventional RNAi and antisense technologies. These compounds have enhanced drug-like properties such as spontaneous cellular uptake, serum stability, reduced potential for off-target immune stimulation and long-lasting intracellular activity.

“Using our proprietary sd-rxRNA technology, MirImmune demonstrated the unique applicability of sd-rxRNA for immune checkpoint modulation in cellular immuno-oncology therapies,” Dr. Cauwenbergh adds. “The advantages of our platform, including the potential to silence multiple checkpoints at the same time, set RXi apart from other pharmaceutical and biotech companies. With the acquisition of MirImmune, we anticipate that evaluating our RNAi platform in the immuno-oncology space will open up novel and better therapeutic approaches for treatment of some of the more difficult-to-treat cancers.”