Scientists from Peking University have recently created a gene-editing technique that has great potential in treating disease. This technique, known as LEAPER, is similar to CRISPR-Cas13 in its ability to edit RNA rather than DNA; however, the Peking researchers feel that LEAPER presents several advantages over the CRISPR-Cas13 technique. Their findings were published recently in Nature Biotechnology.
LEAPER (leveraging endogenous ADAR for programmable editing of RNA) is analogous to the Cas13 protein with its ability to target strands of RNA, but the two differ in that Cas13 relies on both a guide RNA and the Cas13 enzyme to manipulate RNA. This new technique sets itself apart by using only one component, known as arRNA, to do so. This simplicity makes LEAPER easier to deliver and less likely to cause undesirable side effects.
This novel approach uses engineered strands of RNA that recruit the ADAR enzyme to swap out different compounds in RNA, effectively editing the molecule. The research team notes that LEAPER circumvents some issues that arise from current gene-editing techniques, including immune responses and other side effects. LEAPER is an efficient and accurate tool that can be used on a variety of cell types, as per the Peking scientists.
“There are clear prospects for using this technology in disease treatment,” said study author Zhou Zhuo of Peking University’s School of Life Sciences. Zhuo explained that LEAPER was used to switch adenosine for guanosine, two nucleotide bases that function as RNA ‘building blocks,’ in their trials. He went on to say that this switching of bases could potentially treat almost half of all known hereditary disorders.
Hurler syndrome, a severe and rare genetic disorder that is associated with reduced life expectancy and various complications, is one of these diseases that was used in Zhuo and colleagues’ research. The team extracted cells from patients with the condition and found that LEAPER was effective in restoring functional enzyme activity in these cells.
This was done not by editing the faulty gene that coded for this mutated enzyme, but rather by altering the RNA that is transcribed from this gene. Genes are used to create RNA, which is the used as a template to synthesize proteins, like enzymes. LEAPER’s function is to edit this transcribed RNA before it is read to create a protein, therefore the technique promotes synthesis of the proper enzyme.
Though this technique shows promise, it still has a way to go. Ernst Wolvetang of the Australian Institute for Bioengineering and Nanotechnology noted that LEAPER’s mechanism may not be applicable to certain cell types and that undesired genetic changes may manifest. This technique will need to be proven in animal studies as well before the team can consider moving into clinical trials.
Wolvetang did, however, praise LEAPER for its simplified approach compared to other genetic-editing techniques. He claimed that using only arRNA rather than Cas and a guide RNA makes the compound much easier to deliver.
Other techniques have been developed in China that were said to rival CRISPR in editing genetic material, with the “NgAgo” technique initially showing promise but falling short in follow up studies. In more controversial news, the Chinese researcher He Jiankui announced last year that he had used CRISPR technology to genetically edit two children before they were born. He received severe backlash for doing so, however there is now a Russian biologist aspiring to follow suit.
— Exponential Medicine (@ExponentialMed) July 20, 2019