Moligo Technologies and Nationwide Children's Hospital Collaborate to Advance Cystic Fibrosis Research Using Ultrapure Long Single-Stranded DNA

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Oct 24, 2023, 07:30 ET

Project evaluates single-stranded DNA as non-viral delivery vehicle for cell and gene therapies

STOCKHOLM, Oct. 24, 2023 /PRNewswire/ -- Moligo Technologies announced today that it has signed a collaboration agreement with Nationwide Children's Hospital to provide long, single-stranded DNA for its research into gene therapies for cystic fibrosis (CF) and other airway diseases. Moligo's patent-pending enzymatic DNA production technology delivers ultrapure, long ssDDNA at industrial sale - with the ability to introduce chemical modifications - making it potentially suited as a non-viral delivery method in cell and gene therapies.

While significant advances have been made in gene therapy, using the approach for airway diseases is still in the early stages. In cystic fibrosis, the most common genetic airway disease, gene therapy researchers have predominantly focused on replacing the genetic mutation in the CFTR (cystic fibrosis transmembrane conductance regulator) gene for CF with a correct version of the gene using an adeno-associated virus (AAV) as a delivery vehicle. However, CFTR is a relatively long gene, and AAV's capacity for carrying long, therapeutic genes is limited because of its small genome size, creating challenges to AAV delivery.

"If we can successfully use ssDNA to insert large genes, such as CFTR, into airways, the possibilities are endless. There are few options outside of AAV right now in the genome-editing field," said Sriram Vaidyanthathan, Ph.D., a principal investigator at Nationwide Children's Hospital Center for Gene Therapy at the Abigail Wexner Research Institute. "Although the efficiency of editing and producing ssDNA capable of carrying long genes has been a challenge, Moligo's ssDNA has several characteristics that make it a possible option - including its length, ability to be produced at scale, and the fact that it can be chemically modified to potentially improve the stability of the gene."

Vaidyanathan's genome-edited airway stem cell therapy approach involves transplanting corrected airway stem cells into the airways to treat CF and various airway diseases. Although double-stranded DNA (dsDNA) is also a non-viral gene delivery option, research has shown it carries a higher risk than ssDNA that the stem cells will launch an immune response, killing the replacement gene. Over the next year, Vaidyanthathan will conduct a proof-of-concept in vitro study using ssDNA and, if successful, will launch a follow-up study.

"We are extremely pleased to collaborate with Nationwide Children's Hospital on this critical research," said Moligo CEO Cosimo Ducani, Ph.D. "While significant advances have been made in treating cystic fibrosis, many patients with rare genetic mutations don't benefit from current treatments. A gene therapy approach could treat more patients and, importantly, holds the potential for a permanent cure. More broadly, ssDNA could offer a valuable, scalable alternative to current gene therapy approaches, particularly when the gene exceeds the packaging capacity of AAV."

Moligo utilizes a proprietary, PCR-free, enzymatic technology to produce ultrapure DNA strands over 10,000 bases long, 100 percent sequence-verified, and at scale. The process also enables any sequence to be synthesized, overcoming complexity-related barriers. Traditional chemical methods of making ssDNA generate fragments that are too short, have high error rates, and deliver too low quantities. Sequence complexity is also a significant challenge, making encoding many complete and functional long therapeutic genes into ssDNA impossible.

About Moligo Technologies
Moligo Technologies produces long, ultrapure, complex DNA at industrial scale using a proprietary enzymatic synthesis process to overcome the challenges of chemical methods. The company's patent-pending PCR-free "injection-molding" platform can be scaled to produce kilograms of DNA, enough material to enable any cell- or gene-based therapy to go from the lab through clinical trials. With a specialty in complex, ultrapure single-stranded DNA 100 percent sequence verified and more than 10,000 bases long - and at scalable volume - Moligo helps companies take safer, more effective gene-based therapeutics, vaccines, and diagnostics over the finish line and to the patient. Moligo was founded in 2019 and is privately held.

SOURCE Moligo Technologies