A new form of CRISPR genome editing  technique , called as “prime editing”, has been developed which can potentially correct up to 89% of genetic errors. The new approach has been invented by combining the two most important proteins- CRISPR-cas9 and Reverse Transcriptase– in a single machine.

The invention, led by David Liu at Broad Institute of MIT and Andrew Anzalone, postdoctoral fellow in Liu’s lab, was published in the Nature recently.

The technique called” prime editing” is capable of directly editing human cells in a precise, efficient, and highly versatile fashion. The approach expands the scope of gene editing for biological and therapeutics research.

“A major aspiration in the molecular life sciences is the ability to precisely make any change to the genome in any location. We think prime editing brings us closer to that goal,” says David Liu

The new CRISPR “Prime Editing”

Prime editing differs from previous genome-editing systems in that it uses RNA to direct the insertion of new DNA sequences in human cells.

Cas9 disrupt target genes at a specific location and then make it possible to add new sequences through recombination of new DNA into the site, directed by the cell itself. Base editors can perform a chemical reaction to perform a single base change in DNA. Current base editors can only change C-to-T, T-to-C, A-to-G, and G-to-A

Adapted from Broad Insitute (Click to expand)

The new prime editing system involves coupling Cas9 to a different protein called reverse transcriptase. The molecular complex uses one strand of the target DNA site to “prime,” or initiate, the direct writing of edited genetic information into the genome.

A new type of engineered guide RNA, called a pegRNA, directs the prime editor to its target site, where a modified Cas9 cuts one strand of the DNA. The pegRNA also contains additional RNA nucleotides encoding the new edited sequence. To transfer this information, the reverse transcriptase element reads the RNA extension and writes the corresponding DNA nucleotides into the target spot.

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Efficiency demonstrated

In the research paper, Liu and his team have demonstrated the prime editing’s ability to successfully and precisely correct the variant causing sickle cell anemia and Tay sachs disease.

When making precision changes, the researchers report that prime editing achieves successful edits with a lower rate of undesired “off-target” changes when compared to approaches that require making nearby breaks on each DNA strand.Career in Biotechnology

Way forward?

Liu’s team will continue optimizing the technique to maximize its efficiency in different cell types, potential side effects and testing in cell and animal models

Original article: Anzalone AV, et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature. Online October 21, 2019.

The information is adapted fits original source Broad Institute News (https://www.broadinstitute.org/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells)

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