Prime Editing Feasibility
EXPLORATORYPrime editing (PE2/PE3/PEmax) assessment for SMA: SMN2 C6T correction (the root cause fix), ISS-N1 disruption (permanent nusinersen), and ESE strengthening. Compared with approved therapies. Prime editing = reverse transcriptase + Cas9 nickase + pegRNA — no double-strand breaks.
▶How does prime editing design work?
Prime editing couples a Cas9 H840A nickase to an engineered reverse transcriptase. The pegRNA contains a spacer, a primer binding site (PBS), and an RT template (RTT) encoding the desired edit. The nickase cuts one strand; the RT extends the free 3′ end using the RTT as template, writing the edit into the genome.
Feasibility score integrates PE chemistry preferences (nick offset, PBS/RTT length), delivery viability (cargo fits dual AAV or LNP mRNA), and biological plausibility. Efficiencies reflect published PE2/PE3/ PEmax rates for similar edits (15–45% in vivo).