What is CRISPR?
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a natural immune system found in bacteria. When a bacterium survives a viral attack, it stores a fragment of the virus's DNA in its own genome as a "memory". If the virus attacks again, the bacterium uses that memory to recognise and destroy it.
In 2012, Jennifer Doudna and Emmanuelle Charpentier showed that this system — paired with the Cas9 protein — could be reprogrammed to cut any DNA sequence, not just viral DNA. They shared the 2020 Nobel Prize in Chemistry for the discovery.
How does the editing work?
Three components are needed: a guide RNA (gRNA) designed to match the target DNA sequence, the Cas9 protein that does the cutting, and a repair template if a new sequence is to be inserted.
- The gRNA binds to Cas9 and guides it to the matching DNA sequence.
- Cas9 makes a double-strand break — cutting both strands of the DNA helix.
- The cell's own repair machinery fixes the break via one of two pathways: NHEJ (non-homologous end joining), which is imprecise and often disables the gene; or HDR (homology-directed repair), which uses a provided template to insert a precise new sequence.
The guide RNA is simply a short strand of synthetic RNA. Designing one for a new target takes hours rather than months, making CRISPR far faster to deploy than earlier gene-editing tools like zinc-finger nucleases.
See our cells and organelles guide for background on the nucleus where this editing takes place.
Clinical applications
In November 2023, Casgevy (exagamglogene autotemcel) became the first CRISPR therapy approved by the US FDA and UK MHRA. It targets sickle-cell disease and beta-thalassaemia by editing patients' own haematopoietic stem cells to restore functional haemoglobin production.
Ongoing clinical trials are exploring CRISPR for:
- Certain blood cancers (CAR-T cell therapies)
- Leber congenital amaurosis (inherited blindness)
- Transthyretin amyloidosis (a protein-folding disease)
- HIV — silencing the viral reservoir in infected cells
Challenges and ethics
Off-target edits remain the primary technical concern. Cas9 can occasionally cut at unintended sites that partially match the guide RNA — with unknown consequences. Newer variants (high-fidelity Cas9, base editors, prime editors) reduce but do not eliminate this risk.
Germline editing — editing embryos or sperm and egg cells so changes pass to children — is currently banned in most countries after the 2018 case in which He Jiankui produced the first CRISPR-edited babies without proper consent or oversight. The scientific and ethical consensus is that germline editing in humans is premature.
Access and cost are a growing concern. Casgevy is priced at approximately $2.2 million per patient. Without structural solutions, the benefits of CRISPR medicine may remain unavailable to most of the world.