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.
Prime Editors are designed to produce edits across many tissues, organs and types of cells and to work broadly across most types of gene mutations at the natural genomic location, while minimizing unwanted DNA modifications. This approach uses a process designed to produce a wide variety of precise, predictable and efficient genetic outcomes at the targeted sequence, which we believe will dramatically increase the impact of gene editing for a broad range of therapeutic applications.
How Prime Editing Works
Programmable for both search & replace
Exemplary Prime Editing process using Cas and RT. Abbreviations: pegRNA = Prime Editing guide RNA; RT = reverse transcriptase; Cas = CRISPR associated protein
- 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
prime editing can correct all twelve potential base pair mutations
Convert any base pair into any other
Mutated base pairs can be substituted
Extra base pairs can be removed
Missing base pairs can be inserted
We believe Prime Editing can make diverse sequence edits at nearly any desired location in the human genome, enabling multiple therapeutic applications. Prime Editors are able to change any base pair to any other base pair to correct all twelve types of single base pair point mutations, delete DNA sequences to correct insertion mutations, or insert DNA sequences to correct deletion mutations. Prime Editors also have the ability to make direct corrections of DNA, alter the regulatory regions of genes, insert or create premature stop codons, and modify splicing sequences.
one prime editing pegRNA can precisely correct the individual mutations found across many patients
Abbreviations: pegRNA = Prime Editing guide RNA.
Prime Editing is designed to make only the right edit at the right position within a gene, which greatly minimizes on-target by-products at the site of editing, and results in low, or minimal off-target editing in other places in the genome. Our Prime Editors do not create double-stranded DNA breaks, which supports the precision of our technology. Prime Editing requires three “edit checks” or places where there must be a match between the editor and the target DNA in order to complete an edit, which we believe also leads to highly specific and precise edits.
prime editing corrections occur at the natural place in the genome and are permanent
We believe that with a single treatment, Prime Editing could create permanent, positive corrections of disease-causing mutations, resulting in restoration of the gene back to its wild-type healthy sequence. A corrected gene would persist in an edited cell, working naturally and being passed along to daughter cells, leading to a potentially durable cure or therapeutic outcome. These benefits have the potential for optimal gene regulation, which we believe could result in long-lasting benefits to patients.
prime editing can be delivered to the right place in the body using multiple modalities
Prime-Edited cell therapy
Prime Editing is a compelling approach for a wide range of therapeutic applications at the genomic level, and can make precise, targeted edits in an array of cell types, tissues and organs. We believe this breadth in applications and ability to target multiple cell types will enable Prime Editing to bring potentially curative gene editing approaches to a broader set of diseases, beyond genetic disease and towards severe, chronic, and acute diseases.
Programmable large DNA deletion, replacement, integration, and inversion with twin prime editing and site-specific recombinases
Andrew V. Anzalone, Xin D. Gao, Christopher J. Podracky, Andrew T. Nelson, Luke W. Koblan, Aditya Raguram, Jonathan M. Levy, Jaron A.M. Mercer & David R. Liu
Engineered pegRNAs improve prime editing efficiency
James W. Nelson, Peyton B. Randolph, Simon P. Shen, Kelcee A. Everette, Peter J. Chen, Andrew V. Anzalone, Meirui An, Gregory A. Newby, Jonathan C. Chen, Alvin Hsu & David R. Liu
Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors
Andrew V. Anzalone, Luke W. Koblan & David R. Liu