CAMP4 Platform May Enhance Gene Activity to Therapeutic Levels
That is according to new preclinical data shared by scientists from CAMP4 at the 17th Annual Meeting of the Oligonucleotide Therapeutics Society, held virtually Sept. 26–29. The data was discussed in a presentation, titled “Oligonucleotide Mediated Upregulation of Serping1 By Targeting Regulatory RNAs.”
Another presentation from CAMP4 also indicated that its platform could increase the activity of a gene that is defective in some urea cycle disorders, a group of severe and life-threatening liver diseases.
“With the results of these studies, we have the early proof points that our novel approach to harness the power of regRNA for gene upregulation works across multiple genes, fueling our conviction as we advance the development of precise, potent, programmable and durable therapeutics for genetic diseases that lack disease-modifying therapies,” David Bumcrot, PhD, chief scientific officer of CAMP4, said in a press release.
RegRNAs are a recently discovered type of RNA that modulate gene expression upstream of mRNA transcription. In other words, they change how DNA in the cell is “read,” which influences the activity of genes.
CAMP4’s RNA Actuating Platform relies on identifying the specific regRNAs that regulate the activity of a particular gene of interest, then designing oligonucleotides — short pieces of DNA or RNA — that can target these regRNAs to change the activity of the gene.
According to CAMP4, this platform offers a unique approach to increase gene expression in a tunable manner, having potential application in a broad range of diseases.
Most cases of HAE are caused by mutations in a gene called SERPING1, which is mainly made in the liver and that helps to regulate swelling. Abnormally low activity of this gene leads to out-of-control swelling.
Data shared at the meeting showed that, in mouse liver cells, treatment with oligonucleotides designed with CAMP4’s platform led SERPING1 activity to increase by 2–3 times. Furthermore, when the oligonucleotides were injected subcutaneously (under-the-skin) in male mice, there was a significant increase in levels of the protein encoded by SERPING1 in the animals’ blood.
“These data demonstrate that by using oligonucleotides to target regRNA, we can directly upregulate endogenous gene expression at the transcriptional level and achieve a therapeutically relevant result,” Bumcrot said.