(a) Abbreviations for prime editor variants used in
this figure. (b) Targeted insertion and deletion edits with PE1
at the HEK3 locus. (c-h) Comparison of 18
prime editor constructs containing M-MLV RT variants for their ability to
install (c) a +2 G•C-to-C•G transversion edit at
HEK3, (d) a 24-bp FLAG insertion at the +1
position of HEK3, (e) a +1
C•G-to-A•T transversion edit at RNF2,
(f) a +1 G•C-to-C•G transversion edit at
EMX1, (g) a +2 T•A-to-A•T
transversion edit at HBB, and (h) a +1
G•C-to-C•G transversion edit at FANCF.
(i-n) Comparison of four prime editor constructs containing
M-MLV variants for their ability to install the edits shown in (c-h) in a
second round of independent experiments. (o-s) PE2 editing
efficiency at five genomic loci with varying PBS lengths. (o)
+1 T•A-to-A•T at HEK3. (p) +5
G•C-to-T•A at EMX1. (q) +5
G•C-to-T•A at FANCF. (r) +1
C•G-to-A•T at RNF2. (s) +2
G•C-to-T•A at HEK4. Editing efficiencies
reflect sequencing reads that contain the intended edit and do not contain
indels among all treated cells, with no sorting. Values and error bars
reflect mean±s.d. of n=3 independent biological replicates.