Nanoparticle Delivery of Stabilized Synthetic Transcriptional Repressors for Targeted Gene Regulation

SUMMARY

Enhanced control of disease-associated gene expression through nanoparticle delivery of stabilized DNA-binding peptides and miniproteins, improving targeted transcriptional regulation 

The Unmet Need: Efficient and specific delivery of transcriptional regulators to modulate disease gene expression remains a critical challenge

• Current therapeutic approaches to regulate gene expression often suffer from delivery inefficiencies, poor pharmacokinetics, and limited target specificity, reducing their effectiveness in treating diseases such as cancer. The ability to precisely control transcription in vivo is hampered by inadequate delivery systems for synthetic transcriptional repressors, limiting therapeutic impact and clinical translation potential.

• Advances in nanomedicine and synthetic biology have generated growing interest in nanoparticle-mediated delivery platforms combined with engineered biologics to achieve targeted and controlled gene modulation, creating new opportunities for next-generation therapeutics that address complex transcriptional dysregulation in diseases.

The Proposed Solution: Nanoparticle-encapsulated synthetic transcriptional repressors enhance in vivo gene regulation and therapeutic efficacy

• The faculty inventor developed nanoparticle formulations that encapsulate stabilized synthetic DNA-binding peptides and miniproteins, referred to as synthetic transcriptional repressors (STRs), to improve pharmacokinetics and targeting of disease-relevant genes.

• This approach builds upon prior STR platforms by offering enhanced delivery and tissue penetration, demonstrated through increased regulation of target gene expression and anti-tumor efficacy in mouse tumor models. Unlike existing methods, these nanoparticle systems provide improved control of transcriptional repression.

ADVANTAGES

• Improved pharmacokinetics and biodistribution

• Enhanced target gene expression regulation

• Nanoparticle-mediated synthetic peptide delivery

• Increased anti-tumor efficacy in preclinical models

• Compatibility with existing STR platforms

APPLICATIONS

• Targeted transcriptional repression in metastatic colorectal cancer

• Gene expression modulation in cancer immunotherapy

• Therapeutic regulation of oncogenic pathways in solid tumors