Inside EE’s Newest Research Grants: Tackling the Barriers to CF Breakthroughs
Six newly funded projects are pursuing promising solutions to some of the field’s toughest challenges for the final 10%.
Getting gene-editing tools through thick CF mucus. Helping genetically corrected cells survive and rebuild healthy tissue. Breaking down the defenses of resistant bacteria—and even finding ways to make antibiotics work again.
These are some of the challenges researchers are tackling through Emily’s Entourage’s (EE) newest round of research funding.
Across six new Translational Research Grants, scientists are developing technologies to overcome critical hurdles in genetic therapies while pursuing new approaches to combat persistent, drug-resistant lung infections.
The strategies are different, but the goal is the same: turn promising science into tangible breakthroughs for the final 10% of people with cystic fibrosis (CF) unable to benefit from current mutation-targeted therapies.
Here’s a closer look at what EE’s newest funded researchers are working on—and why it matters.
Getting Through CF Mucus
Xizhen Lian, PhD, Johns Hopkins University, with Justin Hanes, PhD
Thick, sticky CF mucus can block therapies from reaching the cells they’re designed to treat. Drs. Lian and Hanes are developing tiny delivery vehicles called lipid nanoparticles (LNPs) specifically designed to move through mucus and carry gene-editing therapies directly to airway cells.
Why it matters: Getting through the mucus barrier could help unleash genetic therapies capable of treating CF at its source.
Building a Better Delivery Vehicle
Zheng-Rong Lu, PhD, Case Western Reserve University
Dr. Lu is developing a new type of biodegradable LNP designed to safely and efficiently carry gene-editing machinery directly into cells. The team will initially test the approach in a mouse model with a nonsense mutation, evaluating whether it can successfully correct and restore CFTR function.
Why it matters: Gene editing can only become a viable treatment if the tools can safely reach and enter the cells where they’re needed. This project aims to help bridge that gap.
Putting AI to Work
Jacob Witten, PhD, Massachusetts Institute of Technology
Dr. Witten is using artificial intelligence (AI) and advanced laboratory models of lung biology to rapidly screen and identify LNPs designed specifically for inhaled genetic therapies. The goal is to find delivery systems that improve potency, reduce toxicity, and are capable of penetrating CF mucus to efficiently deliver their therapeutic cargo.
Why it matters: Using AI to accelerate the search for better delivery systems will enable researchers to exponentially increase the number of LNPs they screen while reducing the cost of these screenings.
Helping Corrected Cells Take Hold
Sriram Vaidyanathan, PhD, Nationwide Children’s Hospital and The Ohio State University, with Kyle Cromer, PhD, University of California, San Francisco
Drs. Vaidyanathan and Cromer are developing engineered “synthetic receptors” that temporarily give corrected airway stem cells a growth advantage that can be turned on and off. The goal is to help those repaired cells grow, repopulate, and ultimately repair the airway.
Why it matters: Helping corrected cells persist and rebuild tissue could make future gene-based therapies that restore lung health in all people with CF more durable.
Breaking Down Bacteria’s Defenses
Hugh Smyth, PhD, The University of Texas at Austin
Dr. Smyth is developing an inhaled therapy for methicillin-resistant Staphylococcus aureus (MRSA) that pairs an antibiotic with a biofilm dispersing enzyme that breaks down the protective biofilms bacteria use to survive. Delivering the two together could help the antibiotic more effectively kill bacteria that can be life-threatening and are difficult to treat.
Why it matters: Breaking down the bacteria’s defenses while simultaneously attacking it with an antibiotic could provide a more effective way to treat persistent, life-threatening MRSA infections.
Making Antibiotics Work Again
David T. Pride, MD, PhD, University of California San Diego School of Medicine
Dr. Pride is pairing antibiotics with bacteriophages—or “phages,” viruses found in the environment that specifically target and kill harmful bacteria—to tackle drug-resistant Achromobacter infections, which are a growing problem in people with CF. Early findings show that certain phage-antibiotic combinations can eliminate and even resensitize previously resistant bacteria to antibiotics regardless of their previous susceptibility.
Why it matters: If phages can help restore the effectiveness of previously resistant antibiotics, this approach could create new treatment options for people facing some of the most difficult-to-treat CF infections.
Explore all Emily’s Entourage awarded grants → https://www.emilysentourage.org/awarded-grants/
