Engineering genomes

Genome engineering gives an organism a new function, or changes or removes an existing one, by adding or removing genes.

Transposons, or 'jumping genes', are pieces of DNA that can move from one place in a genome to another, mostly by a cut-and-paste mechanism. Scientists can engineer a transposon to land in a chosen gene. Its insertion breaks the coding frame, so the gene no longer works: a knock-out. An insertion can also carry new DNA in: a knock-in. Organisms made this way serve as models for understanding disease and developing drugs.

Genome editing goes further: it can add, remove or change a specific DNA sequence at an exact place. The most powerful tool is CRISPR-Cas9, borrowed from bacteria. Bacteria keep pieces of DNA from viruses that once attacked them, as a memory; if the same virus attacks again, they use these memories to find and destroy its DNA.

How it works:

• A guide RNA is made with two parts: one that matches the target DNA, and one that binds the enzyme Cas9.
• The guide RNA leads Cas9 to the matching place in the genome, and Cas9, an endonuclease, makes a double-strand break there.
• The cell then repairs the break. If it simply joins the ends, small errors usually knock out the gene. If scientists supply a template with the desired edit, the cell copies it in by homologous repair, making the exact change.

In short: the guide RNA finds it, Cas9 cuts it, and the cell repairs it the way you want. Emmanuelle Charpentier and Jennifer Doudna won the 2020 Nobel Prize in Chemistry for developing it; Charpentier had discovered a key RNA (tracrRNA) while studying Streptococcus pyogenes.