Science Article Highlights ReCode Therapeutics’ Lung Delivery and CFTR Gene Correction Potential

ReCode Therapeutics, based in Menlo Park, California, is a clinical-stage company specializing in genetic medicines. The organization has recently published a significant research article in the journal Science, titled "In vivo editing of lung stem cells for durable gene correction in mice." This publication highlights the effectiveness of their Selective Organ Targeting (SORT) lipid nanoparticles (LNPs) in achieving high levels of persistent gene editing in lung stem cells through systemic intravenous delivery.

The research, led by Professor Daniel Siegwart, Ph.D., who is both a lead author and co-founder of ReCode Therapeutics, was conducted in collaboration with researchers from UT Southwestern and ReCode. The team developed SORT LNPs that efficiently direct gene-editing tools away from the liver and specifically to cells in the lung. This innovation marks a significant milestone in the field of genetic medicine, demonstrating the potential for lasting disease-modifying therapies.

One of the key findings of the study is the successful delivery of gene editors to lung stem cells. This is the first instance where LNPs carrying gene-editing tools have been shown to effectively correct genes in lung stem cells through systemic circulation. Lung stem cells are crucial because they are progenitors for numerous functional cells in the lung, which are implicated in various rare genetic diseases like cystic fibrosis (CF) and primary ciliary dyskinesia (PCD).

The study achieved over 70% editing efficiency in mouse lung stem cells, with effects lasting up to 660 days. If these results can be replicated in clinical settings, they may offer long-term benefits for patients with genetic lung diseases. This approach could lead to new, durable treatments for conditions that are currently not adequately addressed by existing therapies.

A significant breakthrough demonstrated in the study is the proof of concept for correcting the CF mutation CFTR R553X, which small molecule therapies cannot treat. The new technique restored CFTR protein function in cells derived from CF patients, suggesting a potential path for durable cystic fibrosis treatment.

Dr. Marco Weinberg, Head of Research at ReCode, emphasized the importance of these findings, noting that achieving long-lasting gene correction in lung stem cells underscores the growing potential of SORT LNPs for delivering effective treatments for conditions like cystic fibrosis. This research highlights the scientific vision and collaboration within the ReCode team to develop the SORT LNP platform, aimed at achieving targeted delivery of genetic medicines for lung disorders.

These promising results bolster ReCode's ongoing efforts to translate SORT LNP-based gene editing into clinical applications, potentially leading to durable and curative therapies for patients with genetic lung disorders. However, further studies are required to understand the mechanisms behind efficient delivery to airway stem cells, ensure safety and tolerability in larger animal models, and evaluate efficacy in human trials.

ReCode Therapeutics continues to advance its pipeline, focusing on developing therapies for a range of rare and common genetic diseases, including musculoskeletal, central nervous system, liver, and infectious diseases. The company has been recognized as a Best Place to Work by the San Francisco Business Times and Silicon Valley Business Journal.

ReCode’s proprietary SORT LNP platform represents a significant advancement in the precision delivery of genetic medicines, potentially improving efficacy and potency by targeting specific organs, tissues, and cells implicated in various diseases. Their lead programs, RCT1100 and RCT2100, target primary ciliary dyskinesia and cystic fibrosis, respectively, utilizing inhaled, mRNA-based therapies formulated with the SORT LNP delivery platform.