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 present disclosure provides systems, compositions, and methods for simultaneously editing both strands of a double-stranded DNA sequence at a target site to be edited.”— U.S. Patent No. 12,031,126 source

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.