Beta-sitosterol lipid nanoparticles for aerosolized gene editing in lung diseases

Background

Cystic fibrosis (CF) is a life-threatening genetic disorder caused by mutations in the CFTR gene, leading to progressive lung dysfunction. A particularly challenging mutation, W1282X, introduces a premature stop codon that results in non-functional CFTR protein. Patients with this mutation are largely unresponsive to current small molecule treatments, highlighting a critical unmet medical need.
While gene editing offers a promising solution, delivery to lung epithelial cells is complicated by the need for localized, safe, and efficient delivery systems. Traditional lipid nanoparticles (LNPs) degrade under aerosolization stress, limiting their effectiveness for pulmonary gene therapy.

Technology overview

This technology presents an advanced LNP platform, designated B-1-1, for aerosolized delivery of gene editing agents targeting CF mutations such as W1282X. The LNP composition replaces conventional cholesterol with β-sitosterol, and includes an ionizable lipid, phospholipid, and polymer-conjugated lipid. The formulation encapsulates mRNA encoding adenine base editors and guide RNAs for precise correction of single-nucleotide mutations in the CFTR gene.
The system is optimized for nebulization, ensuring structural integrity and efficient delivery to lung epithelial cells. β-sitosterol substitution enhances endosomal escape and maintains gene editing activity even after exposure to shear stress, overcoming a key limitation of traditional LNPs. This approach enables localized, high-efficiency delivery to the lungs while minimizing systemic toxicity, positioning it as a transformative therapy for CF patients with currently untreatable genotypes.

Benefits

  • Maintains LNP integrity and gene editing efficacy after aerosolization
  • Enhances endosomal escape using β-sitosterol for improved delivery
  • Enables localized treatment of lung epithelial cells with minimal systemic exposure
  • Corrects CFTR nonsense mutations, including W1282X, unresponsive to small molecules
  • Supports precise single-base gene correction using mRNA and guide RNAs

Applications

  • Cystic fibrosis gene therapy
  • Pulmonary delivery of gene editing agents
  • Nebulized LNP formulations
  • Precision medicine for genetic lung diseases
  • mRNA delivery systems for respiratory disorders

Opportunity

  • Addresses a critical gap in treatment for CF patients with nonsense mutations
  • Differentiated by aerosol stability and enhanced delivery performance
  • Aligns with growing demand for targeted, non-invasive genetic therapies
  • Available for exclusive licensing

Intellectual property

PCT/US2025/022486
Patent Information:
Direct Link:
https://canberra-ip.technologypublisher.com/tech/Beta-sitosterol_lipid_nanopa rticles_for_aerosolized_gene_editing_in_lung_diseases
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For Information, Contact:
Cory Lago
Intellectual Property Specialist
University of Texas at Austin
cory.lago@austin.utexas.edu