Columbia Technology Ventures

Modified peptide nucleic acids for highly specific suppression of oncogene transcription

This technology is a peptide nucleic acid (PNA) oligomer and single-terminus delivery peptide conjugate that minimizes non-specific cell toxicity and can be used as a cancer therapeutic.

Unmet Need: Therapeutics for carcinomas with minimized non-specific cytotoxicity

The current standard of care for cancer involves aggressive treatments like radiation, chemotherapy, and small-molecule inhibitors, which have extensive off-target side effects. Peptide nucleic acids (PNAs) are an alternative treatment for cancer because they selectively hybridize with cancerous DNA and RNA. This hybridization suppresses transcription and thus the proliferation of cancer cells. Since PNAs specifically target cancer cells, they offer a therapeutic approach for cancer with minimized toxicity for healthy tissues.

The Technology: Biomolecular conjugate for specific suppression of KRAS G12D transcription

This technology is a cancer therapeutic that improves the delivery and target stabilization of peptide nucleic acids (PNAs). The delivery peptide sequence consists of lysine residues with a hydrophobic/cationic chain on one end of the PNA oligomer, which increases the potency of transcription suppression. This PNA oligomer design also reduces non-specific toxicity in healthy cells, and thus may increase the efficacy of cancer treatment.

This technology has been validated in vitro in human cancer cell lines AsPC1 (KRAS G12D-expressing cells) and BxPC3 (KRAS WT-expressing cells).

Applications:

  • Therapeutic method to increase dosage, efficacy, and delivery of peptide nucleic acid (PNA) agents
  • Therapeutic for cancer targeting tumor-specific genetic mutations
  • Research tool and delivery platform to reduce the expression of specific genes
  • Diagnostic tool for the labeling and detection of target DNA sequences

Advantages:

  • Minimizes non-specific cell toxicity in peptide nucleic acid (PNA)-based therapeutics
  • Increases cancer treatment efficacy by targeting tumor-specific gene mutations
  • Reduces PNA-peptide conjugate agglomeration
  • Reduces steric interference of delivery peptides conjugated with PNA oligomers
  • Improves kinetic binding of PNA to the target oncogene

Lead Inventor:

Jeffrey H. Rothman, M.D., Ph.D.

Patent Information:

Patent Pending (US20220144898)

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