Rumpa B. Bhattacharjee1, Mirko Hennig1, Daniella Ishimaru1, David Liston1, Jackson K. Eby2, Christian C. Corona1, Ishita Agarwal1 Jade E. Casillas1, Shohan Molla1, Maninder S. Sidhu1, Julia Poniatowski1, Sierra R. Comini1, Ally Ashworth1, Xueliang Yu2, Peiyang Gao2, Harriet E. Lister1, Omid Mousa1, Hannah L. Golliher3, Patrick R. Sears3, Weining Yin3, Michael J. Torres2, Daniel J. Siegwart4, Vladimir G. Kharitonov1, Lawrence E. Ostrowski3, David J. Lockhart1, Brandon A. Wustman1
1 ReCode Therapeutics, Inc., Menlo Park, CA,
2 ReCode Therapeutics, Inc., Dallas, TX,
3 Dept of Cell Biology and Physiology, UNC-Chapel Hill, NC, 4UT Southwestern Medical Center, Dallas, TX
Rescue of Ciliary Function in Cell-based Primary Ciliary Dyskinesia Models using Nebulized, LNP-formulated mRNA ReCode Therapeutics is developing an mRNA-based therapy for the treatment of PCD caused by mutations in DNAI1. The DNAI1 mRNA is sequence optimized and formulated in a proprietary SORT lipid nanoparticle (LNP). The LNP formulated mRNA is nebulized and delivered as an aerosol directly into the airway by using a VITROCELL® Cloud 12. Using knockdown human bronchial epithelial (hBE) cultures and knockout mouse tracheal cultures we show that ReCode’s LNP can restore ciliary activity.
Primary ciliary dyskinesia (PCD) is a rare genetic respiratory disease caused by inherited mutations in more than 40 different genes. Bi-allelic mutations in any of the PCD genes result in loss of ciliary activity and mucociliary clearance. People with PCD suffer from recurrent respiratory tract infections and inflammation leading to bronchiectasis with varying severity.
Currently, there are no disease-modifying therapies available, and treatments are limited to palliative care for the management of symptoms. Thus, there is a clear unmet medical need for therapeutic approaches to treat the underlying causes of PCD.