A method inserts up to 12.5 kilobases without a double-strand break
Donor-complementary prime editing inserted DNA segments as long as 12.5 kilobases in cultured cells without a double-strand break, and one guide pair also handled pooled variant libraries. A separate method used a mild electrical pulse to label proteins inside living cells. In flies, a conserved beat-and-side gene code still routed olfactory neurons when one matched pair was disrupted. The findings widen the reach of biological targeting tools without establishing therapeutic success.
Science··Night
Long DNA segments land without a double-strand break
A peer-reviewed Nature Biotechnology study tackles the untidy repair that can follow when both DNA strands are cut to place a long sequence at a chosen genomic site. The method, called donor-complementary prime editing, pairs donor DNA carrying a single-stranded overhang with two matching guide RNAs and a prime-editing enzyme. It made precise insertions of up to 12.5 kilobases in cultured cells. The same guide pair also accepted donor pools assembled from synthesised oligonucleotides, enabling broad variant screens at amino-acid and nucleotide resolution in a target region of the EGFP reporter gene. That library compatibility could reduce the need to design a new guide for every edit; the paper reports no therapeutic-delivery experiment.[1]
An electrical pulse switches on a protein tag at the chosen moment
A peer-reviewed Nature Chemistry study used cyclopropanol as a chemical handle for marking proteins inside cells at a chosen moment without reacting beforehand. The molecule stayed inert under physiological conditions; a mild electrochemical stimulus then created a reactive group in place and labelled proteins for imaging and mass-spectrometry analysis. Instead of favouring the cysteines and lysines commonly targeted by bioconjugation methods, the tag preferred acidic residues such as glutamate and aspartate inside water-repelling pockets. The researchers also built a choline-based version that entered membrane-lipid metabolism and labelled membrane-associated proteins. This selectivity reaches different parts of the proteome, while the demonstrations remain confined to cultured cells.[2]
A fly wiring code absorbs one broken match
A peer-reviewed PLOS Biology study found that each class of olfactory receptor neuron in Drosophila and its partner projection neuron carries a distinctive combination of beat and side genes. A lineage-specific expression programme first establishes a shared template, then produces different combinations within that lineage. When researchers disrupted the matched Beat-IIa and Side-IV pair, connections showed no obvious mistargeting in the glomeruli, fitting an error-tolerant adhesion code better than a one-to-one lock and key. Similar expression patterns in two insects that diverged from Drosophila 260–300 million years ago point to deep evolutionary roots. The genes still matter: knocking down side reduced synaptic density across the antennal lobe.[3]
