(a) pegRNAs contain a spacer sequence, an sgRNA
scaffold, and a 3’ extension containing a reverse transcription (RT)
template (purple), which contains the edited base(s) (red), and a
primer-binding site (PBS, green). The primer-binding site hybridizes to the
nicked target DNA strand. The RT template is homologous to the DNA sequence
downstream of the nick, with the exception of the encoded edited base(s).
(b) Installation of a T•A-to-A•T transversion
at the HEK3 site in HEK293T cells using Cas9 H840A nickase
fused to wild-type M-MLV reverse transcriptase (PE1) and pegRNAs with
varying PBS lengths. (c) T•A-to-A•T transversion
editing efficiency and indel generation by PE1 at the +1 position of
HEK3 using pegRNAs containing 10-nt RT templates and a
PBS sequences ranging from 8-17 nt. (d)
G•C-to-T•A transversion editing efficiency and indel
generation by PE1 at the +5 position of EMX1 using pegRNAs
containing 13-nt Rt templates and a PBS sequences ranging from 9-17 nt.
(e) G•C-to-T•A transversion editing
efficiency and indel generation by PE1 at the +5 position of
FANCF using pegRNAs containing 17-nt RT templates and a
pBs sequences ranging from 8-17 nt. (f)
C•G-to-A•T transversion editing efficiency and indel
generation by PE1 at the +1 position of RNF2 using pegRNAs
containing 11 -nt RT templates and a PBS sequences ranging from 9-17 nt.
(g) G•C-to-T•A transversion editing
efficiency and indel generation by PE1 at the +2 position of
HEK4 using pegRNAs containing 13-nt RT templates and a
PBS sequences ranging from 7-15 nt. (h) PE1-mediated +1 T
deletion, +1 A insertion, and +1 CTT insertion at the HEK3
site using a 13-nt PBS and 10-nt RT template. Sequences of pegRNAs are those
used in Fig. 2a (see Supplementary Table 3). 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.