Pioneering small interfering RNA (siRNA) technology developed by chemist Anastasia Kuborova, Ph.D. Lemondi Family Chair in Biomedical Research Hassan Fakih, Ph.D., a professor of RNA therapeutics at Mass. Chan School of Medicine and a postdoc in her lab, is licensed by Mass. Chan from PLaN Therapeutics, a nonprofit biotechnology company wholly owned by the PLN Foundation.

This collaboration aims to further develop allele-specific siRNA-based therapies for the treatment of PLN-R14del inherited cardiomyopathy. Under the agreement, PLaN Therapeutics will retain exclusive rights to the product.

“We are excited to partner with PLaN Therapeutics to develop potential siRNA therapeutics for PLN-R14del cardiomyopathy,” said Dr. Fakih. “PlaN’s expertise in PLN-R14del cardiomyopathy will help move this science from the clinical setting to the clinical setting where it will benefit patients and their families.”

“This collaboration is an important step in translating decades of groundbreaking scientific research into a potential treatment for patients with PLN-R14del cardiomyopathy,” said PLaN Therapeutics CEO Pavlina Konstantinova. “It offers hope to patients and families who currently have few options.”

PLN-R14del cardiomyopathy is caused by a dominant inherited mutation in the phospholamban (PLN) gene, leading to progressive heart failure and life-threatening arrhythmias. Currently, the disease is treated with common heart failure drugs, but this does not affect the progression of the disease. As symptoms progress, end-stage heart failure invariably develops, and the only treatment is heart transplantation.

siRNAs are short double-stranded RNA molecules (approximately 20-25 base pairs) that silence specific genes by targeting complementary messenger RNA (mRNA) for post-transcriptional degradation, thereby preventing translation. Essentially, siRNAs are of great interest in translational biomedical research because they can knock down genes of interest. However, delivery of siRNA to target tissues such as the heart has been challenging as potential off-target side effects and lack of chemical durability limit efficiency and efficacy.

Under this collaboration agreement, PLaN Therapeutics will work closely with Dr. Khvorova and Dr. Fakih to develop clinically validated chemical modifications of allele-specific siRNA molecules that selectively suppress mutated PLN genes without interfering with expression of healthy alleles.

By modifying specific chemical groups, researchers aim to improve important therapeutic properties such as durability, distribution, and target engagement. Researchers will focus on identifying, optimizing, and further developing the most effective allele-specific siRNA molecules to address the PLN-R14del mutation. This approach is intended to support a subcutaneous dosing regimen approximately once every 2 to 3 months, potentially offering a patient-friendly treatment profile.

“With our technology, we can create siRNA oligonucleotides that can reach the heart,” Kuborova said. “This study is a major step toward solving the problem of siRNA delivery in the heart and brings us one step closer to clinical treatment of PLN-R14del cardiomyopathy.”

PLaN Therapeutics is a nonprofit biotechnology company focused on developing disease-modifying therapies for PLN-R14del cardiomyopathy. The company, which originates from the PLN Foundation, is focused on translating cutting-edge science into treatments that address the root causes of this genetic heart disease. PLaN Therapeutics is committed to providing PLN-R14del patients with this therapy at a reasonable price.