Genetic Therapies for the Final 10%: What’s Coming Into Focus
For years, the potential for development of genetic therapy has been a source of cautious hope for the cystic fibrosis (CF) community—especially for those in the final 10% who don’t benefit from current CFTR modulators. Over the years, research has advanced significantly and recently, multiple genetic therapies have advanced to clinical trials.
With all the new progress and updates, there are—understandably—lots of questions about these therapies—the promise, the challenges, the timelines, and much more! To address those questions, as well as to update the community about research presented during our most recent scientific symposium, Emily’s Entourage (EE) hosted a special webinar—Gene Therapy Updates in CF: Scientific Symposium Recap and Q&A—sharing the latest developments and what they mean for those in the final 10%.
The event featured three leading CF researchers and clinicians:
- Jennifer Taylor-Cousar, MD, MSCS, ATSF, National Jewish Health
- Patrick Harrison, PhD, Cincinnati Children’s Hospital Medical Center
- Paul McCray, Jr., MD, University of Iowa
Moderated by Chandra Ghose, PhD, Chief Scientific Officer at EE, the conversation offered a clear-eyed look at CF genetic therapies—from exciting advances and innovative strategies to the challenges still ahead.
Key Takeaways: What’s Coming Into Focus
While the science behind genetic therapies is complex, the core message from our expert panel was clear: we’re closer than ever before. These advancements are not just theoretical anymore—they are taking shape in labs and clinical research centers, offering genuine hope for those in the final 10%.
1. Gene Editing Tools Are Rewriting What’s Possible
In the laboratory, gene editing tools like CRISPR, base editing, and prime editing are now making it possible to precisely correct mutations in the CFTR gene at the DNA level. This represents a major leap beyond existing treatments that only manage symptoms—they have the potential to fix the root cause of CF itself.
Some approaches have already demonstrated promising results in lab-grown cells and animal models. While challenges like delivery to lung cells and ensuring the edits last remain, these advances raise the possibility of a one-time, permanent treatment in the future.
2. Delivery Remains the Next Great Frontier
The ability to fix or replace faulty genes is just one part of the equation. The other—and arguably greater—challenge is delivering these therapies effectively to lung cells, the primary site of CF damage.
The lungs present a uniquely difficult environment: thick mucus, inflammation, and the body’s immune defenses all act as barriers that can degrade or block treatments. To tackle this, researchers are developing and testing a variety of delivery vehicles, including:
- Lipid nanoparticles (LNPs): Tiny fat-based carriers similar to those used in COVID-19 vaccines, designed to deliver mRNA via inhalation.
- Viral vectors: Modified viruses that can safely insert DNA or RNA into target cells.
- Virus-like particles and peptides: Engineered to mimic viruses without triggering strong immune reactions.
In addition, scientists are exploring ways to improve therapy access to cells using existing CF treatments like hypertonic saline, which can thin mucus and enhance delivery.
3. Starting Treatment Before Birth
One of the most striking discussions focused on in-utero therapy—treating CF before a baby is even born.
Early animal studies suggest that delivering treatment during pregnancy could protect organs like the lungs, pancreas, and reproductive system from early damage. For example, following treatment with CFTR modulators, some models showed improved pancreatic function at birth and a much lower incidence of complications like meconium ileus. These results have also been reported in case studies in people.
As we consider the future possibility of administering genetic therapies in utero, the fetal environment offers unique advantages. As examples, a more tolerant immune system, easier access to stem cells, and a smaller body size that allows therapies to reach more tissues with less medication. For the fetus identified with CF in utero (usually by the 2nd trimester), such therapy could potentially reverse some of the damage that occurred early in pregnancy and prevent further damage from occurring.
Real-World Glimpse: In Utero CF Treatment
Curious what this could look like in practice? One couple shared how they used CFTR modulators during pregnancy—under medical supervision—to improve health outcomes for their daughter with CF. Read their story on the EE blog.
4. Clinical Trials Are Already Underway
There are more genetic therapy trials actively recruiting or in progress now than ever before. These studies cover a range of approaches, including LNP delivered mRNA therapies, DNA delivery, and various viral vectors designed to carry corrected genetic instructions into cells.
Importantly, many of these therapies are mutation-agnostic, meaning they aim to be effective for all people with CF, regardless of mutation. This also includes those that don’t benefit from existing CFTR modulators, such as those with rare and nonsense mutations. Though these trials are still in early phases and results are uncertain and will take time, the fact that they are now being tested in trials represents real progress and hope, especially for those in the final 10% who have long been left without options.
5. There’s So Much to Consider—And That’s Okay
Choosing to participate in a gene therapy trial is a personal decision and comes with many considerations. In addition to thinking about safety, potential benefits, and dosing, participants also have to consider practical factors: time away from work or school, travel to trial sites, child care, eligibility based on health status or mutation type, and potential impacts on current therapies like modulators. Panelists emphasized that it’s normal—and expected—to have questions and concerns.
Tools like CF Clinical Trial Connect (CTC)—a global patient database created by Emily’s Entourage—are designed to help match individuals with trial opportunities that may be a good fit, based on their unique profile. Coupled with support from care teams, trial coordinators, and community advocates, individuals can make informed choices that align with their health and lifestyle needs.
Q&A Summary: Your Most Pressing Questions, Answered
Below is a collection of key questions from the event and a few we didn’t have time to cover—all answered by our expert panelists.
Q: Why hasn’t gene therapy been developed for CF yet, and which organs do current therapies target?
A: Gene therapy for CF is particularly challenging because thick mucus, inflammation, and immune defenses make it difficult to deliver treatments to the lungs. Most current trials focus on the lungs, where CF causes the most severe symptoms, though future therapies may target other organs like the pancreas or liver.
Q: Are genetic therapies mutation-specific, and what progress is being made toward treatments for the remaining 10%?
A: Many, but not all genetic therapies in clinical trials are mutation-agnostic, meaning they should work for all CF mutations, including rare and nonsense mutations in the final 10%. As of July 2025, multiple genetic-based treatments—such as gene therapy, mRNA, (both mutation agnostic) and antisense oligonucleotides (mutation specific)—are in clinical trials now, with preliminary data expected within 12 to 18 months.
Q: What should participants expect in terms of time commitments, eligibility for future trials, and travel support?
A: Trial requirements vary: mRNA therapies currently in testing require frequent visits over weeks, while gene therapies in testing are single-dose with longer follow-ups. Participating in certain trials could affect eligibility for others, especially gene therapy trials using viral vectors. Many trials offer travel assistance, and participants often receive compensation for travel, accommodations, and time off from work.
Q: What are the known risks and side effects of genetic therapies, and can these treatments be administered more than once if needed?
A: Risks and the ability to re-administer genetic therapies vary by technology. For example, trials using lentiviruses aim for long-term benefit from a single dose, but require 15 years of safety monitoring due to the potential rare risks from gene integration. For gene editing therapies (not yet in clinical trials CF), it’s unclear if repeat dosing will be needed—especially if long-lasting progenitor cells are successfully targeted. These answers will become clearer as trials progress.
Q: With many non-viral delivery methods emerging, why are viral vectors still being pursued?
A: Both viral and non-viral delivery methods have pros and cons. Viral vectors form the basis of multiple currently approved genetic therapies for diseases outside of CF. Non-viral vectors for inhalation show promise in lab studies but their safety and effectiveness in humans are not yet proven. Viral vectors may be better suited for certain therapies, including some gene editing approaches. Clinical trials will clarify the best methods.
Q: What are realistic expectations for genetic therapy outcomes compared to CFTR modulators, and what if a therapy doesn’t work?
A: Regulatory approval may require a modest lung function improvement—around 2–4% increase in FEV1, similar to early CFTR modulators. If safety issues arise, independent committees oversee trial adjustments. If a therapy shows no benefit, researchers analyze data to identify causes like delivery or dosage problems. It is important to pursue multiple therapeutic approaches to diversify our portfolio and maximize our chances for success.
Q: How does global access to gene therapies vary by location?
A: It’s likely too early to know exactly how access to CF gene therapies will vary globally. However, looking at gene therapies for other diseases, some sponsors have begun exploring mechanisms to support broader international access.
Q: Are there any inhaled ENaC blockers currently used for CF lung disease?
A: Currently, no inhaled ENaC blockers are approved for treating CF lung disease.
Real Hope, Real Work Ahead
For years, the final 10% has waited—hoping, yearning, and enduring, while they have watched their CF friends’ lives radically transform with the introduction of CFTR modulators. Gene therapy has felt close, but not quite here. But now, that’s changing.
Much work remains—questions to answer, trials to complete, challenges to solve. But real options are emerging, and momentum is building—driven by brilliant scientists, dedicated clinicians, and brave, resilient people with CF who refuse to accept the current CF therapeutic landscape as status quo.
At Emily’s Entourage, we’re racing forward—for the breakthroughs ahead, the lives they will change, and the belief that no one should be left behind. We can’t possibly get there fast enough.
Watch the Full Webinar
If you missed the event or want to rewatch key moments, the full recording is now available:
