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Gene Editing Strategies for the Treatment of Surfactant Protein C Deficiency

Funder Wellcome Charity-funded
Recipient organisation University of Oxford
Funding Not disclosed
Period Oct 2025 — Sept 2028

In plain English

AI plain-English summary

Every breath a person with Surfactant Protein C deficiency takes is a struggle, because their lungs lack a protein that stops the tiny air sacs from collapsing. This rare genetic disease can kill newborns or cause lifelong breathing problems, and the only cure—a lung transplant—often fails when the body rejects the new organ. The researcher is developing two gene-editing approaches to fix the root cause. One strategy corrects the most common disease-causing mutation, found in about 30% of patients, using precise base or prime editing. The other uses mutation-agnostic methods to replace the faulty gene with a healthy copy, no matter which mutation a patient carries. The researcher will also analyse data from the 100,000 Genomes Project to find additional mutations that influence how severely the disease progresses. If successful, these therapies could transform treatment for a life-limiting disorder, offering a permanent genetic fix instead of a temporary transplant. This is fundamental science with a clear therapeutic target—one that could eventually move from the lab bench to a clinical trial for a patient group with no other options.

View original technical description
Surfactant Protein C (SP-C), encoded by the SFTPC gene, is a critical component of pulmonary surfactant, produced in alveolar epithelial cells to reduce surface tension and prevent alveolar collapse. Mutations in SFTPC cause SP-C deficiency, a rare genetic lung disease with highly variable penetrance, ranging from lethal neonatal respiratory failure to milder respiratory symptoms in adulthood. With no cure beyond lung transplantation, which often succumbs to rejection, there is an urgent need for novel therapies addressing the underlying genetic cause. This project aims to develop gene therapies for SP-C deficiency via two strategies: precise and mutation-agnostic. First, I will use advanced base and prime editing strategies to correct the most common variant, I73T, found in ~30% of patients. Secondly, mutation-agnostic methods such as HITI, eePASSIGE, or STITCHR will be applied to replace the mutant gene with a healthy copy, regardless of genotype. Finally, I will uncover additional pathogenic mutations contributing to disease progression and variable penetrance by analysing data from the 100,000 Genomes Project. This insight will inform personalised therapies, targeting both SFTPC and modifier genes, and will prioritise patients most in need of treatment, offering transformative potential for those affected by this life-limiting disorder.

View the original record at the funder ↗

Researchers

Elena Tybulewicz (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Gene Therapy for Surfactant Disorders
Respiratory Gene Therapy Portfolio (RGTP)
Development of a CRISPR/Cas9 gene editing platform to correct Severe Combined Immunodeficiency caused by mutations in the IL7RA gene
The role of aberrant membrane trafficking in pulmonary fibrosis
Targeted gene addition strategies for the treatment of Primary Immunodeficiencies using X-linked lymphoproliferative disease (XLP) as a model

Original classification

PhD Studentship (Basic)

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