Using a human-derived enzyme to safely insert missing DNA into genes

Programmable Mitochondrial DNA Annealase for Scarless, Human-Endogenous Genome Editing and Functional Screening

NIH-funded research Stanford University · NIH-11306501

Creating a human-based gene-editing tool to safely and precisely add large pieces of DNA into patient cells with genetic problems.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionStanford University NIH-funded
Lab location1 site (Stanford, United States)
Project IDNIH-11306501 on NIH RePORTER

What this research studies

Researchers are engineering a human protein called Twinkle to act like a DNA inserter that can place large DNA segments into the cell's own genes without cutting the DNA. They plan to guide this human-derived tool with gene-targeting molecules and test it in lab-grown human cells and organoids to see how well it works. The team aims to reduce immune reactions and off-target damage that can happen with non-human editing systems, and to make the system small enough for delivery into patient cells. Work will include functional screening to find the best versions and delivery methods before any human treatments are considered.

Who could benefit from this research

Good fit: Ultimately, people with inherited genetic conditions caused by missing or faulty large DNA segments could be candidates for therapies developed from this work.

Not a fit: This is laboratory-stage research, so people with conditions unrelated to gene defects or those seeking immediate treatment would not benefit now.

Why it matters

Potential benefit: If successful, this could enable safer, less immunogenic ways to correct genetic defects by inserting large DNA sequences into patient cells.

How similar studies have performed: Prior non-human tools like CRISPR-based transposases and phage recombineering have enabled large DNA insertion but faced immune and delivery limits, while using a human Twinkle enzyme is a novel and less-tested approach.

Where this research is happening

Stanford, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.