Prime editing rewrites DNA without a double-strand break, but the first generation edited one strand and leaned on the cell to resolve the mismatch. US12031126B2 and US11912985B2 - both "Methods and compositions for simultaneous editing of both strands of a target double-stranded nucleotide sequence," issued 2024 to The Broad Institute (inventors include Liu and Anzalone) - claim editing both strands at once.
The load-bearing limitation is in the title: simultaneous dual-strand editing. Single-strand prime editing installs the edit on one strand and depends on cellular mismatch repair to copy it to the other - a step that can fail or revert. The claimed method edits both strands directly, improving the efficiency and durability of the installed edit.
The CPC profile confirms the prime-editing lineage: C12N 9/1276 (reverse transcriptase) is the hallmark of prime editing, where a reverse transcriptase templated by a pegRNA writes the new sequence. Paired with C12N 15/102 (editing methods) and C12N 9/22 (Cas component), the tags describe a prime-editing system extended to act on both strands.
Why does dual-strand editing decide scope? Because the inventive step over the foundational prime-editing claims is precisely the both-strands mechanism. A competitor practicing single-strand prime editing may be outside a claim drawn to simultaneous dual-strand editing; the limitation both distinguishes the prior single-strand art and confines the claim to the dual-strand improvement.
For the landscape, this is the Broad's prime-editing estate maturing - the foundational architecture (Liu/Anzalone) extended by improvement claims like dual-strand editing. Freedom-to-operate for any prime-editing program now means clearing not just the base architecture but the improvement layer, and the dual-strand grants are a defining piece of that second layer.