Abstract: Provided are fusion proteins that include an apolipoprotein B mRNA editing enzyme catalytic subunit 3A (APOBEC3A) and a clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) protein, optionally further with uracil glycosylase inhibitor (UGI). Such a fusion protein is able to conduct base editing in DNA by deaminating cytosine to uracil, even when the cytosine is in a GpC context or is methylated.

Abstract: Provided are fusion proteins that include an apolipoprotein B mRNA editing enzyme catalytic subunit 3A (APOBEC3A) and a clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) protein, optionally further with uracil glycosylase inhibitor (UGI). Such a fusion protein is able to conduct base editing in DNA by deaminating cytosine to uracil, even when the cytosine is in a GpC context or is methylated.

Abstract: Provided are fusion proteins and related molecules useful for conducting base editing with reduced or no off-target mutations. The fusion protein may include a first fragment comprising a nucleobase deaminase or a catalytic domain thereof, a second fragment comprising a nucleobase deaminase inhibitor, and a protease cleavage site between the first fragment and the second fragment. Also provided are improved prime editing systems, including prime editing guide RNA with improved stability.

Abstract: Provided are fusion proteins and related molecules useful for conducting base editing with reduced or no off-target mutations. The fusion protein may include a first fragment comprising a nucleobase deaminase or a catalytic domain thereof, a second fragment comprising a nucleobase deaminase inhibitor, and a protease cleavage site between the first fragment and the second fragment. Also provided are improved prime editing systems, including prime editing guide RNA with improved stability.

Abstract: A fusion protein which may comprise a first nCas9 fragment, a chimeric insertion fragment, a second nCas9 fragment and two UGI fragments from N-terminus to C-terminus, wherein the chimeric insertion fragment is selected from APOBEC1 fragment or APOBEC3A fragment for cytosine deamination at the target site. The fusion protein may comprise a first nCas9 fragment, a chimeric insertion fragment and a second nCas9 fragment from N-terminus to C-terminus, wherein the chimeric insertion fragment is TadA-TadA* for cytosine deamination at the target site. The present disclosure provides a novel base editing tool that is compatible with insertion of various deaminases on the chimeric sites of nCas9. Compared with nCas9 terminal fusion base editor, the base editing tool of the present invention significantly reduce off-targeting on both DNA and RNA, while maintaining specific targeted base editing efficiency, with higher specificity and favorable industrialization prospects.

Abstract: Provided are fusion proteins and related molecules useful for conducting base editing with reduced or no off-target mutations. The fusion protein may include a first fragment comprising a nucleobase deaminase or a catalytic domain thereof, a second fragment comprising a nucleobase deaminase inhibitor, and a protease cleavage site between the first fragment and the second fragment. Also provided are improved prime editing systems, including prime editing guide RNA with improved stability.

Abstract: The present disclosure relates to the field of biotechnology, in particular to a base editing tool and use thereof. The present disclosure provides a fusion protein comprising a first nCas9 fragment, a chimeric insertion fragment, a second nCas9 fragment and two UGI fragments from N-terminus to C-terminus, wherein the chimeric insertion fragment is selected from APOBEC1 fragment or APOBEC3A fragment. The present disclosure provides a novel base editing tool that is compatible with insertion of various deaminases on the chimeric sites of nCas9. Compared with nCas9 terminal fusion base editor, the base editing tool of the present invention significantly reduce of off-targeting on both DNA and RNA, while maintaining specific targeted base editing efficiency, with higher specificity and favorable industrialization prospects.

Abstract: Provided are fusion proteins and related molecules useful for conducting base editing with reduced or no off-target mutations. The fusion proteins may include a first fragment comprising a nucleobase deaminase or a catalytic domain thereof, a second fragment comprising a nucleobase deaminase inhibitory domain, and a protease cleavage site between the first fragment and the second fragment. Also provided are improved prime editing systems, including prime editing guide RNA with improved stability.

Abstract: Provided are fusion proteins and related molecules useful for conducting base editing with reduced or no off-target mutations. The fusion proteins may include a first fragment comprising a nucleobase deaminase or a catalytic domain thereof, a second fragment comprising a nucleobase deaminase inhibitory domain, and a protease cleavage site between the first fragment and the second fragment. Also provided are improved prime editing systems, including prime editing guide RNA with improved stability.

Abstract: A reagent and a method for repairing an FBN1T7498C mutation by using base editing. A kit for efficiently repairing the FBN1T7498C mutation is characterized by comprising a base editor and a repair re-sgRNA directed to the FBN1T7498C site. A base editing technology is used to repair the mutation of FBN1T7498C through a precise CT single base mutation, thereby providing a method for treating a Marfan syndrome caused by such mutation.

Abstract: Provided are fusion proteins that include an apolipoprotein B mRNA editing enzyme catalytic subunit 3A (APOBEC3A) and a clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) protein, optionally further with uracil glycosylase inhibitor (UGI). Such a fusion protein is able to conduct base editing in DNA by deaminating cytosine to uracil, even when the cytosine is in a GpC context or is methylated.

Abstract: Provided are base editors containing a cytidine and a catalytically inactive version of Lachnospiraceae bacterium Cpf1 (LbCpf1). The new base editors have greatly improved editing efficiency and fidelity as compared to Cas9-based base editors, and have different editing windows.