Utilize lipid nanoparticle-based CRISPR/Cas9 genome editing to delete the Pfkp gene for the treatment of head and neck cancer

Background:

Head and neck cancer continues to pose a significant clinical challenge due to its aggressive nature and poor patient prognosis. A primary contributing factor is the overexpression of the epidermal growth factor receptor (EGFR), which limits the efficacy of current treatments such as Cetuximab. There is a clear need for innovative therapeutic strategies that can directly target the molecular drivers of this cancer to improve treatment outcomes. The development of targeted genome editing methods, particularly those utilizing CRISPR/Cas9 technology, offers promising avenues to address this unmet medical need.

Technology Overview:

This invention leverages cutting-edge lipid nanoparticle (LNP) technology to deliver the CRISPR/Cas9 genome editing system, specifically engineered to disrupt the Pfkp gene, which plays a critical role in the progression of head and neck cancer. Utilizing a self-assembly approach, Cas9 mRNA and a single-guide RNA (sgPfkp) are encapsulated within LNPs, creating a stable and efficient delivery vehicle. Upon administration, the LNPs facilitate targeted delivery and cellular uptake of the CRISPR components, enabling precise editing of the Pfkp gene in tumor cells. This targeted genome editing leads to a marked decrease in Pfkp expression, which correlates with significant tumor reduction demonstrated in mouse models. The method employs a non-viral delivery system, enhancing safety and reducing potential immunogenicity compared to viral vectors. The novelty and value of this technology reside in its integration of LNP delivery with CRISPR/Cas9 genome editing for cancer therapy, which allows for precise genetic intervention without modifying existing intellectual properties. This approach demonstrates not only the feasibility of targeting oncogenes through genome editing but also offers a highly adaptable platform for treating various cancers with genetic underpinnings.

Advantages:

•    Highly targeted genome editing focusing on the Pfkp gene, reducing off-target effects.
•    Efficient and safe delivery via lipid nanoparticles, minimizing immune response and toxicity.
•    Demonstrated significant tumor reduction in preclinical mouse models, validating therapeutic potential.
•    Non-viral delivery system enhances safety profile compared to traditional viral vectors.
•    Potentially adaptable platform technology for treating other genetically driven diseases beyond head and neck cancer.
•    Independence from existing intellectual property simplifies licensing and commercialization pathways.

Applications:

•    Treatment of head and neck cancer by targeted in vivo genome editing.
•    Development of next-generation therapies for cancers linked to specific genetic abnormalities.
•    Use as a research tool to better understand gene function in cancer progression.
•    Potential expansion to other solid tumors through modification of target genes and sgRNAs.
•    Application in personalized medicine by tailoring genome editing components to individual patient genetic profiles.

Intellectual Property Summary:

Patent application filed, PCT/US2026/019670

Stage of Development:

TRL 3 – Experimental Proof of Concept

Licensing Status:

This technology is available for licensing.