Fig. 4: Off-target evaluation of PNLM-pcABE. | Nature Communications

Fig. 4: Off-target evaluation of PNLM-pcABE.

From: Protein-nucleic acid language model-assisted design of precise and compact adenine base editor

Fig. 4: Off-target evaluation of PNLM-pcABE.The alternative text for this image may have been generated using AI.

a Cas9-dependent DNA on and off-target analysis at the indicated targets (HEK site2、PD-1-sg4、PCSK9-sg1 and HAAVR-sg4) of ABE8e, ABE9 and PNLM-pcABE in HEK293T cells. Data are mean ± s.d. (n  =  3 independent experiments) and p values were determined by a two-tailed Student’s t-test (ABE8e vs PNLM-pcABE: for HEK site2, p < 0.0001 at GUIDE-seq-OT1, p = 0.0002 at CHIP-seq-OT1, p = 0.0002 at CHIP-seq-OT3, p <0.0001 at CHIP-seq-OT5; for PD-1-sg4, p = 0.0023 at OT5, p = 0.0021 at OT7, p = 0.4904 at OT10). b Cas9-independent DNA off-target analysis of the modified orthogonal R-loop by ABE8e, ABE9 and PNLM-pcABE. Data are mean ± s.d. (n  =  3 independent experiments) and p values were determined by a two-tailed Student’s t-test (ABE8e vs PNLM-pcABE: p <0.0001 at R-loop1, p < 0.0001 at R-loop2, p = 0.0002 at R-loop3, p < 0.0001 at R-loop4, p = 0.0010 at R-loop5, p = 0.0019 at R-loop6). c RNA off-target editing activity by ABE8e, ABE9, PNLM-pcABE using RNA-seq, GFP is a negative control. Each biological replicate is listed on the bottom. Source data are provided as a Source data file.

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