Nanoparticle-Based Gene Editing Could Expand Treatment Options for Cystic Fibrosis

Why It Matters

A durable, genome‑integrated therapy could address the 10% of cystic fibrosis patients unresponsive to existing modulators and reshape delivery strategies for complex genetic diseases.

Key Takeaways

• Lipid nanoparticles delivered full CFTR gene and CRISPR components
• 3‑4% cells corrected, restored up to 100% function
• Platform enables mutation‑agnostic therapy for 1,700 CFTR variants
• Non‑viral delivery avoids immune response and size limits
• Could be adapted for other large‑gene lung diseases

Pulse Analysis

The landscape of genetic medicine has long been dominated by viral vectors, which, despite their efficiency, suffer from payload constraints, manufacturing complexity, and immune‑mediated clearance. Lipid nanoparticles (LNPs), popularized by mRNA COVID‑19 vaccines, offer a non‑viral alternative that can be produced at scale and modified with relative ease. UCLA’s recent work demonstrates that LNPs can be engineered to encapsulate not only messenger RNA but also the bulky CRISPR/Cas9 machinery and a full‑length DNA template, overcoming the “big gene” barrier that has limited previous non‑viral approaches.

In vitro experiments with human airway epithelial cells harboring a severe CFTR mutation showed that the LNP formulation delivered the therapeutic cassette to roughly three to four percent of cells. Remarkably, this modest editing efficiency translated into 88‑100 percent restoration of chloride channel activity, a result attributed to a codon‑optimized CFTR construct that maximizes protein output once integrated. For the roughly ten percent of cystic fibrosis patients who produce negligible CFTR protein and therefore cannot benefit from existing modulators, a one‑time genomic insertion could provide a durable source of functional protein.

The implications extend beyond cystic fibrosis. Because the platform is modular, swapping guide RNAs and donor templates could address other monogenic lung disorders or even diseases in disparate tissues where large genes pose delivery challenges. Moreover, LNPs sidestep the anti‑vector immunity that hampers repeat dosing, potentially enabling iterative refinements or combination therapies. The remaining hurdle is efficient targeting of airway stem cells, which reside beneath thick mucus in CF patients. Overcoming this barrier will be critical for translating the proof‑of‑concept into a lasting, clinically viable therapy.

Nanoparticle-based gene editing could expand treatment options for cystic fibrosis

Feb 18, 2026

Researchers have demonstrated that lipid nanoparticles can package and deliver an entire therapeutic gene along with gene‑editing machinery – a combination of large, complex components that non‑viral carriers haven’t been able to handle before.

Nanowerk News – UCLA researchers have developed a lipid nanoparticle‑based gene‑editing approach capable of inserting an entire healthy gene into human airway cells, restoring key biological function in a laboratory model of cystic fibrosis and establishing a potential new path toward mutation‑agnostic gene therapy for inherited lung diseases.

The study, published in Advanced Functional Materials (“Lipid Nanoparticles for the Delivery of CRISPR/Cas9 Machinery to Enable Site‑Specific Integration of CFTR and Mutation‑Agnostic Disease Rescue”), shows that lipid nanoparticles — tiny fat‑based particles widely used to deliver mRNA vaccines — can be engineered to carry the complex molecular cargo required for precise insertion of a large full‑length gene into the genome without using viral vectors.

Image: Artistic rendering of gene editing reagents — mRNA (red) and DNA (green and yellow) constructs — being packaged into a lipid nanoparticle (blue). (Image: Adalia Zhou)

“This work shows that we can package everything needed for precise gene insertion into a single, non‑viral delivery system,” said Dr. Steven Jonas, senior author of the study and a member of the UCLA Broad Stem Cell Research Center. “That’s a critical step toward developing gene therapies that can work across many different disease‑causing mutations.”

Cystic fibrosis is caused by mutations in a single gene, the cystic fibrosis transmembrane conductance regulator (CFTR), which encodes a channel that helps move chloride and water across the surface of airway cells. When the channel does not function properly, mucus in the lungs becomes thick and sticky, trapping bacteria and leading to chronic infections and progressive lung damage.

Although highly effective drugs known as CFTR modulators have transformed care for many people with cystic fibrosis, about 10 % of patients produce little or no CFTR protein at all, leaving nothing for those drugs to act on.

“For those patients, gene therapy isn’t just an improvement — it’s really the only option,” said Dr. Brigitte Gomperts, co‑author of the study and associate director of translational research at the stem cell center. “You have to give the cell the ability to make the protein in the first place.”

A new way to deliver a complete gene

Since there are over 1,700 different mutations in the CFTR gene that can cause cystic fibrosis, the team looked to develop a universal approach that could correct any of these errors in a single edit rather than individually.

Most experimental gene therapies rely on viral vectors to deliver genetic material into cells. While powerful, viral approaches can be costly to manufacture, limited in the amount of genetic material they can carry and difficult to administer more than once because the immune system can recognize and react to them.

In this study, the UCLA team instead used lipid nanoparticles as a non‑viral delivery system. The particles were engineered to transport three gene‑editing components simultaneously:

1. CRISPR machinery to cut DNA at a precise location,

2. Guide molecules to target the correct genomic site, and

3. A DNA template encoding a full, functional copy of the CFTR gene.

“Getting all of that into a single particle — especially a gene as large as CFTR — is something that hadn’t been shown before,” said Ruth Foley, the study’s first author and a recent Ph.D. graduate from the Jonas lab at UCLA. “If you can solve the ‘big gene’ problem, it opens the door for a lot of other diseases as well.”

The researchers tested the system in lab‑grown human airway cells carrying a severe cystic fibrosis mutation that does not respond to existing drugs. The nanoparticles successfully delivered a healthy CFTR gene into about 3–4 % of the cells.

Despite that relatively small fraction of corrected cells, the treatment restored 88 %–100 % of normal CFTR channel function across the cell population.

The researchers say the strength of that recovery reflects not just where the gene was inserted, but how it was engineered. The replacement CFTR gene was designed to maximize protein production once it entered the cell, enabling even a small number of corrected cells to have an outsized effect. This codon‑optimized design, developed by collaborators in Dr. Donald Kohn’s lab at UCLA, boosts CFTR protein production without altering the protein itself.

Toward durable, one‑time therapies

Unlike approaches that deliver messenger RNA — which must be repeatedly re‑dosed — the new strategy inserts the corrected gene directly into the genome, potentially allowing cells and their descendants to continue producing functional CFTR over time.

For long‑term benefit, however, gene editing ultimately needs to reach airway stem cells, which sit deep within the lung’s protective lining and regenerate the airway throughout a person’s life.

“These stem cells are long‑lived and constantly regenerate the airway,” said Gomperts, who is also a professor of pediatrics and pulmonary medicine at the David Geffen School of Medicine at UCLA. “If you can correct them, you could, in theory, have a lasting source of healthy cells.”

Reaching those cells remains one of the biggest challenges ahead. The airway is designed to block foreign particles, and in patients with cystic fibrosis, thick mucus creates an additional barrier.

“This paper is a proof of concept,” said Jonas, who is also an assistant professor of pediatrics at the medical school and a member of the California NanoSystems Institute. “It shows that we can package and deliver the right genetic cargo. The next challenge is getting it to the right cells in the body.”

A platform with broader implications

Because lipid nanoparticles are modular and do not rely on viral components, the approach could be more flexible, scalable and potentially more affordable than traditional gene therapies.

“This kind of platform gives you room to iterate,” Foley said. “If you need to re‑dose or adapt the cargo for a different disease, you’re not starting from scratch.”

Beyond cystic fibrosis, the researchers say the strategy could be applied to other genetic lung diseases — and potentially conditions in other tissues — caused by large genes with many possible mutations.

“For patients who currently have no effective treatments,” Gomperts said, “this kind of work represents hope — not because it will be ready tomorrow, but because it shows a path forward.”

Source: By Tiare Dunlap, UCLA (Content may be edited for style and length)