The Nobel Prize-winning gene editing technology CRISPR, developed by microbiologist Emmanuelle Charpentier and biochemist Jennifer Doudna, is expected to revolutionize the field of healthcare through its potential to edit genes with unprecedented precision. The breakthrough technology has opened up new possibilities for treating genetic diseases, developing more effective therapies, and even editing the genomes of plants and animals for agricultural and environmental purposes.
The CRISPR-Cas9 system, inspired by a natural defense mechanism found in bacteria, allows scientists to target and edit specific sections of the genetic code with remarkable accuracy, offering hope for personalized medicine tailored to individual genetic profiles. The wide-ranging applications of CRISPR are still being explored, but its impact on human health and well-being is already evident, marking a significant leap forward in the ongoing quest to understand and manipulate the building blocks of life.
CRISPR has opened the path for many more gene editing technologies, and, as it seems, even more advanced ones, such as seekRNA.
Scientists at the University of Sydney developed SeekRNA, which is more accurate and flexible than the accepted norm, CRISPR. In order to streamline editing and lower error rates, SeekRNA makes use of a programmable ribonucleic acid (RNA) strand that can locate insertion sites in genetic sequences directly. A group at the School of Life and Environmental Sciences, under the direction of Dr. Sandro Ataide, is creating the new gene-editing instrument. The publication of their research can be found in Nature Communications.
Dr. Ataide stated, “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”.
“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.”
The double-helix genetic code of life is the target of CRISPR, which depends on breaking it into two strands. Additional proteins or DNA repair machinery are required to insert the new DNA sequence, which can result in errors.
“SeekRNA can precisely cleave the target site and insert the new DNA sequence without the use of any other proteins,” said Dr. Ataide.
SeekRNA originates from the IS1111 and IS110 families of naturally occurring insertion sequences found in bacteria and archaea (nucleus-free cells). These families of insertion sequence proteins have high target specificity, while the majority of them show little to no target selectivity. SeekRNA has used this accuracy to produce its encouraging results thus far.
SeekRNA can be altered to fit any genomic sequence and properly orient the new DNA by using the accuracy of this insertion sequence family. This makes it possible to create an editing tool that is far more accurate and less prone to mistakes.
Dr. Ataide has mentioned, “In the laboratory, we have successfully tested seekRNA in bacteria. Our next steps will be to investigate if the technology can be adapted for the more complex eukaryotic cells found in humans,”.
One benefit of the system is that it can effectively transfer genetic material with just one small protein and one short SeekRNA strand. SeekRNA is composed of an RNA strand with 70–100 nucleotides and a small protein with 350 amino acids. A system of this size could be enclosed in lipid nanoparticles or vesicles to deliver a system of this size to target cells, which are biological nanoscale delivery vehicles.
Another feature that sets SeekRNA apart from other gene editing techniques is its autonomous ability to insert DNA sequences in the desired location—something that many of the editing tools available today are unable to accomplish. There are size restrictions on the genetic sequences that can be introduced using current CRISPR technology, which restricts the scope of application.
Similar investigations into the gene-editing potential of the IS1111 and IS110 families are being conducted by other teams worldwide. Nevertheless, according to Dr. Ataide, they rely on a much larger RNA version and have only demonstrated results for one member of the IS110 family. By using the shorter seekRNA itself and direct laboratory sampling, the Sydney team is improving its methodology.
Since the groundbreaking discovery of CRISPR over a decade ago, gene editing has rapidly advanced into a transformative field, leading to innovative applications across various disciplines. This technology has significantly boosted fruit and crop disease resistance, revolutionized the speed and cost of human disease detection, catalyzed efforts to find a cure for genetic disorders like sickle cell disease, and enabled the development of cutting-edge cancer therapies such as CAR-T cell therapy. With the introduction of emerging technologies like SeekRNA, the capabilities of gene editing are continuously expanding, promising even greater precision and efficiency in altering specific genetic sequences. The dynamic evolution of gene editing not only showcases its immense potential for driving scientific progress but also hints at a future filled with groundbreaking discoveries and opportunities to address complex challenges in agriculture, healthcare, and beyond.