Background

RAS oncogenes are involved in more than 30% of all human cancers and have therefore long been in the searchlight of industry, but have so far remained “undruggable”.

Technology Overview

SDU researchers have devised a new strategy to target HRAS,NRAS and KRAS directly. This approach uses splice-switching oligonucleotides(SSOs).

SSOs have previously been approved for Spinal Muscular Atrophy (SPINRAZA®) and Duchenne Muscular Dystrophy (EXONDYS 51™).
SSOs hold great promise for nucleotide based therapeutics. There is a large range of chemically modified nucleotides already available for the design of stable, bioavailable and non-toxic SSOs.
SDU researchers have designed and optimized several different SSOs that—through exon 2 skipping in HRAS or KRAS—cause significant reduction in growth and proliferation of several cancer cell types (bladder, pancreatic, colorectal, lung, etc.). For instance T24, MiaPaca2, NCI-H1792, NCI-H358, NCI-H23, and SW620 cells lines are reduced in proliferation after treatment with our SSOs.
The researchers have developed mutation specific SSOs, which are able to mediate exon 2 skipping preferentially from the allele with the oncogenic mutation, thus reducing side effects.
Our SSOs perform better than siRNA (silencing RNA)

Figure 1: Mode of action

Stage of Development

Recent experiments in xenografted mice (, ) show that treatment with one of our KRAS SSOs prevents tumor development in mice transplanted with SW620 colorectal cancer cells.
The researchers believe that SSO-based targeting of RAS oncogenes can be developed into new targeted therapies of human cancers, if our unique expertise is combined with the knowledge and techniques used for drug development and delivery in the pharma industry.

Opportunity

We are looking for soft funding and/or company collaborations to use this proprietary technology for developing cancer therapeutics involving RAS mutations including:

Lung, pancreatic and colon cancers (KRAS mutations) – Present focus!
Bladder, head, neck and skin cancers (HRAS mutations) – Potential focus
Melanoma (NRAS mutation is predominate) – Potential focus
Hematological cancers, such as multiple myeloma where NRAS and KRAS mutations are frequent – Potential focus

Splice-Switching Oligonucleotides for Cancer Treatment

Patents

IP Status

Seeking