Nucleic acid-guided DNA synthesis with reverse transcriptases

This technology is a system for guided DNA synthesis with high efficiency and minimal byproducts.

Unmet Need: Specific and precise tools for genome engineering

Current approaches to genome engineering face challenges with specificity, efficiency, and off-target effects, especially for large-scale modifications or larger insertions. Retron-mediated approaches to improve homology-directed repair of CRISPR-Cas9 edits only work for small-scale edits. Prime editing approaches also show low editing efficiencies limited to small template sizes. Non-long-term repeat retrotransposons can perform target-primed reverse transcription and are abundant in nature, making them potential candidates for specific, efficient, and programmable gene editing.

The Technology: Reverse transcriptases for efficient nucleic acid-guided DNA synthesis

This technology describes a tolerable and conserved system found in nature to enable precise template insertion. This technology is also capable of generating concatemeric DNA products by performing “rolling circle” reverse transcription. This technology can complement current genome engineering systems, improving efficiency and specificity. It also has potential for therapeutic and clinical applications.

Applications:

  • Protein or nucleic acid multimerization
  • Biosensing approaches
  • Molecular stopwatch or event timers
  • Can be modified to enable delivery to human cells

Advantages:

  • High efficiency and specificity
  • Avoids undesirable byproducts
  • Allows for the insertion of larger templates
  • Enables large-scale modifications to the genome
  • Generates concatemeric DNA products

Lead Inventor:

Samuel H. Sternberg, Ph.D.

Patent Information:

Patent Pending(WO/2025/101943)

Related Publications:

Tech Ventures Reference:

  • IR CU24147, CU24368, CU25244

  • Licensing Contact: Cynthia Lang