Science

about

Prime Editing is a next-generation gene editing technology that acts like a DNA word processor, with the power to search and replace genetic sequences at their exact location in the genome, all without making double-strand breaks in DNA.

science

How Prime Editing Works

Programmable for both search & replace
prime editing search and replace
prime editing search and replace
prime editing search and replace
prime editing search and replace
prime editing search and replace
Exemplary Prime Editing process using Cas and RT. Abbreviations: pegRNA = Prime Editing guide RNA; RT = reverse transcriptase; Cas = CRISPR associated protein

Key Features

  • Programmable and highly flexible

  • High fidelity and specificity

  • High editing efficiency

  • Minimal off-target activity

  • Potential for improved gene function through in situ editing

  • Edits in multiple clinically relevant rapidly dividing, non-dividing, mammalian, non-mammalian cell types and organs

  • No DNA double-strand breaks

  • Validated by multiple independent research laboratories worldwide

versatile

prime editing can correct all different types of mutations

Point Mutation

Convert any base pair into any other

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Point Mutation

Mutated base pairs can be substituted

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Insertion Mutation

Extra base pairs can be removed

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Deletion Mutation

Missing base pairs can be inserted

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Versatile

Prime Editing can correct almost all types of gene mutations and can be used to modify gene-regulatory sequences. These edits can be made in therapeutically relevant cells and organs, including specialized terminally-differentiated cells. A single Prime Editor can correct the individual mutations found across patients, meaning that Prime Editing can potentially address more than 90% of known disease-causing genetic mutations.

precise

one prime editing pegRNA can precisely correct the individual mutations found across many patients

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Abbreviations: pegRNA = Prime Editing guide RNA.

Precise

Prime Editing occurs with high fidelity, making the correct edit at the exact target site with minimal off-target activity. Prime Editing does not cause double-strand breaks and does not affect cell viability, which may contribute to better patient outcomes, fewer side effects and overall improved safety.

effective

prime editing corrections occur at the natural place in the genome and are permanent

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Effective

Prime Editing makes a permanent correction at the natural place in the genome. As a result, the corrected gene returns to physiologic regulation. This can be especially important where gene dosage is critical to protein function. Other approaches may not faithfully restore gene function. These advantages can provide patients with long-lasting benefit, complete correction and a durable cure.

flexible

prime editing can be delivered to the right place in the body using multiple modalities

Non-viral nanoparticle

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RNA-protein complex

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Viral vector

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Prime-Edited cell therapy

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Flexible

Prime Editing can be delivered via multiple modalities including RNA, DNA, and RNA–protein complexes, unlocking opportunities for genetic medicine. By taking advantage of proven delivery technologies, we can choose the best method to deliver Prime Editing depending on where it needs to go in the body. This flexibility provides opportunities to fix the underlying causes of genetic disorders, treat common diseases, and target cancers with treatments that are easily distributed, manufactured at scale, and re-dosed if necessary.

references

Further reading

  1. Prime editing for functional repair in patient-derived disease models. Schene, I.F., Joore, I.P., Oka, R. et al. Nat Commun 11, 5352 (2020).

Journal | NCBI

  1. Efficient generation of mouse models with the prime editing system. Liu, Y., Li, X., He, S. et al. Cell Discov 6, 27 (2020).

Journal | NCBI

  1. Unbiased investigation of specificities of prime editing systems in human cells. Kim, D.Y., Moon, S.B., Ko, J.-H., et al. Nucleic Acids Res 48, 10576–10589 (2020).

Journal | NCBI

  1. Predicting the efficiency of prime editing guide RNAs in human cells. Kim, H.K., Yu, G., Park, J. et al. Nat Biotechnol 39, 198–206 (2021).

Journal | NCBI

  1. PrimeDesign software for rapid and simplified design of prime editing guide RNAs. Hsu, J.Y., Grünewald, J., Szalay, R. et al. Nat Commun 12, 1034 (2021).

Journal | NCBI

  1. Improved prime editors enable pathogenic allele correction and cancer modelling in adult mice. Liu, P., Liang, SQ., Zheng, C. et al. Nat Commun 12, 2121 (2021).

Journal | NCBI

  1. Genome-wide specificity of prime editors in plants. Jin, S., Lin, Q., Luo, Y. et al. Nat Biotechnol (2021).

Journal | NCBI

  1. Prime editing in mice reveals the essentiality of a single base in driving tissue-specific gene expression. Gao, P., Lyu, Q., Ghanam, A.R. et al. Genome Biol 22, 83 (2021).

Journal | NCBI

  1. Engineered prime editors with PAM flexibility. Kweon, J., Yoon, J.-K., Jang, A.-H., et al. Mol. Ther. 29, 2001-7 (2021).

Journal | NCBI