Title:Evolution of Prime Editing Systems: Move Forward to the Treatment of Hereditary Diseases
Volume: 25
Issue: 1
Author(s): Olga V. Volodina*, Anastasia R. Fabrichnikova, Arina A. Anuchina, Olesya S. Mishina, Alexander V. Lavrov and Svetlana A. Smirnikhina
Affiliation:
- Laboratory of Genome Editing, Research Centre for Medical Genetics, 115522, Moscow, Russia
Keywords:
Prime editing, CRISPR-Cas, mismatch repair, genome editing, FEN1, EXO1.
Abstract: The development of gene therapy using genome editing tools recently became relevant.
With the invention of programmable nucleases, it became possible to treat hereditary diseases due
to introducing targeted double strand break in the genome followed by homology directed repair
(HDR) or non-homologous end-joining (NHEJ) reparation. CRISPR-Cas9 is more efficient and
easier to use in comparison with other programmable nucleases. To improve the efficiency and
safety of this gene editing tool, various modifications CRISPR-Cas9 basis were created in recent
years, such as prime editing – in this system, Cas9 nickase is fused with reverse transcriptase and
guide RNA, which contains a desired correction. Prime editing demonstrates equal or higher correction
efficiency as HDR-mediated editing and much less off-target effect due to inducing nick.
There are several studies in which prime editing is used to correct mutations in which researchers
reported little or no evidence of off-target effects. The system can also be used to functionally
characterize disease variants. However, prime editing still has several limitations that could be further
improved. The effectiveness of the method is not yet high enough to apply it in clinical trials.
Delivery of prime editors is also a big challenge due to their size. In the present article, we observe
the development of the platform, and discuss the candidate proteins for efficiency enhancing,
main delivery methods and current applications of prime editing.
