%0 Journal Article
%T Engineered CRISPR prime editors with compact, untethered reverse transcriptases.
%A Grünewald J
%A Miller BR
%A Szalay RN
%A Cabeceiras PK
%A Woodilla CJ
%A Holtz EJB
%A Petri K
%A Joung JK
%J Nat Biotechnol
%V 41
%N 3
%D 03 2023
%M 36163548
%F 68.164
%R 10.1038/s41587-022-01473-1
%X The CRISPR prime editor PE2 consists of a Streptococcus pyogenes Cas9 nickase (nSpCas9) fused at its C-terminus to a Moloney murine leukemia virus reverse transcriptase (MMLV-RT). Here we show that separated nSpCas9 and MMLV-RT proteins function as efficiently as intact PE2 in human cells. We use this Split-PE system to rapidly identify and engineer more compact prime editor architectures that also broaden the types of RTs used for prime editing.