Gene editing approach targeting lungs shows promise in preclinical study

New Treatment for Cystic Fibrosis: SORT LNP-Based Gene Editing Therapy Corrects CFTR Gene Mutation in Lung Cells

A team of researchers from ReCode Therapeutics carried out a proof-of-concept study that tested a new gene-editing therapy designed to target lung stem cells in mice through an intravenous infusion of Selective Organ Targeting (SORT) lipid nanoparticles (LNPs). The therapy was developed using ReCode’s platform, which aims to enable the human body to create more healthy CFTR protein, an essential protein for regulating the balance of salt and water in cells.

Lung-Targeted SORT LNP Platform for Better Gene Correction Therapy

The first-generation LNPs are mostly taken up by the liver, making it difficult to target specific organs. In response, ReCode developed a revolutionary technology that aims to design LNPs suitable for organs other than the liver. In cystic fibrosis patients, the LNPs have to have the ability to target the lungs, where thick mucus accumulates.

The SORT LNP platform was designed using lipid nanoparticles that help the LNPs get into cells. Also, this versatile platform has been engineered to provide various modes of administration that allow stem cells in the lungs to be efficiently targeted.

Long-Lasting Gene Correction in Lung Cells with the SORT LNP-Based Gene Editing Therapy

In a recent study, the research team tested SORT LNP-based gene editing therapy by correcting a disease-causing CFTR gene mutation in lung cells derived from cystic fibrosis (CF) patients. The study showed that the therapy could achieve gene editing in more than 70% of lung stem cells in mice when delivered through the bloodstream, and over 80% of mature lung epithelial cells had sustained gene correction for 660 days, proving the long-lasting effect of the therapy.

ReCode Therapeutics is also working on the RCT2100 lead candidate, which provides patients with healthy CFTR mRNA, the template molecule used when translating the DNA sequence into protein. Moreover, ReCode is teaming up with Intellia Therapeutics to develop gene-editing therapies for correcting genetic diseases.

Testing of SORT LNP Therapy in Clinical Settings

ReCode’s gene correction approach for cystic fibrosis is currently being tested in a phase 1 clinical trial that involves healthy volunteers intending to move forward with testing in CF patients. The trial aims to prove RCT2100’s efficacy and safety in patients with Class 1 CFTR mutations, who are ineligible for existing CFTR modulator therapy.

The therapy is said to correct defects by more than 95% in cells obtained from CF patients with the R553X mutation and restore CFTR protein function similar to that seen in people with an eligible mutation.

Conclusion

The groundbreaking SORT LNP platform by ReCode Therapeutics has proven effective for developing targeted gene-editing therapies for genetic diseases such as cystic fibrosis. The proof-of-concept study carried out by the team demonstrated sustained gene correction and long-lasting effects of the therapy, providing exciting prospects for more durable treatments.

Originally Post From https://cysticfibrosisnewstoday.com/news/gene-editing-approach-targeting-lungs-shows-promise-preclinical-study/