Beyond CRISPR: seekRNA delivers a new pathway for accurate gene editing

Lead author Rezwan Siddiquee (centre) with Dr Sandro Ataide (left) and Caitlin McCormack in the Ataide Laboratory. Photo: Fiona Wolf/University of Sydney

Scientists at the University of Sydney have developed a gene-editing tool with greater accuracy and flexibility than the industry standard, CRISPR, which has revolutionised genetic engineering in medicine, agriculture and biotechnology.

SeekRNA uses a programmable ribonucleic acid (RNA) strand that can directly identify sites for insertion in genetic sequences, simplifying the editing process and reducing errors.

The new gene-editing tool is being developed by a team led by Dr Sandro Ataide in the School of Life and Environmental Sciences. Their findings have been published in Nature Communications.

“We are tremendously excited by the potential for this technology. SeekRNA’s ability to target selection with precision and flexibility sets the stage for a new era of genetic engineering, surpassing the limitations of current technologies,” Dr Ataide said.

“With CRISPR you need extra components to have a ‘cut-and-paste tool’, whereas the promise of seekRNA is that it is a stand-alone ‘cut-and-paste tool’ with higher accuracy that can deliver a wide range of DNA sequences.”

CRISPR relies on creating a break in both strands of target DNA, the double-helix genetic code of life, and needs other proteins or the DNA repair machinery to insert the new DNA sequence. This can introduce errors.

Dr Ataide said: “SeekRNA can precisely cleave the target site and insert the new DNA sequence without the use of any other proteins.

“This allows for a much cleaner editing tool with higher accuracy and fewer errors.”

Gene-editing has opened completely new areas of research and application since the development of CRISPR more than 10 years ago. It has led to improvements in disease resistance in fruit and crops, reduced the cost and speed of human disease detection, helped in the search for a cure for sickle cell disease and allowed for the development of revolutionary cancer treatment known as (CAR) T-cell therapy.

“We are very much in the early days of what gene editing can do. We hope that by developing this new approach to gene editing, we can contribute to advances in health, agriculture and biotechnology,” said joint author Professor Ruth Hall from the University of Sydney.

Precise genetic targeting

SeekRNA is derived from a family of naturally occurring insertion sequences known as IS1111 and IS110, discovered in bacteria and archaea (cells without a nucleus). Most insertion sequence proteins exhibit little or no target selectivity, however these families exhibit high target specificity.

It is this accuracy that seekRNA has used to achieve its promising results to date.

Using the accuracy from this insertion sequence family, seekRNA can be modified to any genomic sequence and insert the new DNA in a precise orientation.