Gene-editing pioneer calls for big investment in Crispr technology

Expanding medical therapies based on Crispr gene-editing globally is “unrealistic” and the sector needs heavy investment to make the technology, which could transform treatment of diseases, accessible to all, according to its co-discoverer.

Speaking in the wake of last year’s first-ever regulatory approval for a Crispr therapy, Jennifer Doudna, who alongside fellow scientist Emmanuelle Charpentier discovered the gene-editing potential of DNA sequence Crispr-Cas9 in 2012, told the Financial Times she would “love to see the day when Crispr is a standard of care for certain kinds of diseases”.

“We need to really roll up our sleeves and figure out how to take the right steps, both technically and from an investing perspective, to get to the finish line,” she said.

The Crispr genetic code was discovered in bacteria as part of the mechanism that helps the organisms defend themselves against viruses. The Crispr DNA sequence can guide Cas9 — an enzyme that acts like molecular scissors — to specific locations on the genome, allowing scientists to make precise changes to DNA at particular points, removing a gene or tweaking it to change its function.

Biotech companies have worked to apply the technology since Doudna and Charpentier’s discovery. In November, the UK’s medicines and healthcare products regulatory agency gave the world’s first regulatory approval for a Crispr treatment.

The therapy — Casgevy, developed by US biotech company Vertex Pharmaceuticals and Crispr Therapeutics for the blood disorders sickle cell disease and beta thalassaemia — has since been approved by the European Medicines Agency and US Food and Drug Administration.

Sickle cell disease, a genetic blood disorder that causes red blood cells to stretch from a disc to a “sickle” shape, can inhibit blood flow, leading to disorders such as anaemia, painful swelling and strokes.

It predominantly affects people of colour and is prevalent in sub-Saharan Africa, Latin America, the Middle East and India.

But Doudna said it was “unrealistic to think we could deliver[the treatment] globally in the way it’s being provided currently. It’s not going to be possible to do it financially.”

Casgevy involves taking stem cells from patients’ bone marrow, editing them in a laboratory and transplanting them back into the patient.
The process is prohibitively expensive for many health systems. The US list price of the treatment is $2.2mn per dose, while Lyfgenia, another gene therapy for sickle cell disease developed by Bluebird Bio and approved on the same day as Casgevy, costs $3.1mn per dose. Patients require a single treatment.

To lower costs, technology needed to develop “to allow a treatment like Casgevy to be administered in vivo, meaning directly into the body, rather than requiring the laboratory procedure”, said Doudna, who said her California-based Innovative Genomics Institute was focusing on this.

US start-up Intellia Therapeutics has launched the first late-stage trial for an in-vivo Crispr treatment for a rare heart condition.

The costs are also a strain for higher-income countries. Nice, the UK’s healthcare spending watchdog, said last week that it could “accept higher than the usual maximum for assessing cost-effectiveness” of Casgevy but that it needed to collect more data on the drug’s effectiveness before funding it on the NHS.

Other gene therapies that treat rare diseases and have few alternative cures can come with high price tags. The first approved medicine for a rare and fatal genetic disorder in children, metachromatic leukodystrophy, this week became the most expensive drug in history, pricing at $4.25mn.

Doudna said that while “we should be working to get the cost down”, cell and gene therapies can permanently cure patients and lower future healthcare costs, meaning regulators needed to rethink how to price such “one and done” treatments.

Venture capital investment in gene editing dropped last year along with other biotech investments, falling from $2.45bn in 2022 to $1.06bn in 2023, according to data provider PitchBook.

Several early-stage life sciences investors told the Financial Times the technology was attractive but that the field faced a higher bar for investment than other start-ups. “It needs pretty extreme efficacy and needs to be transformational for patients,” one said.

With investment, Doudna said, Crispr could treat more common conditions. She is “bullish” about Crispr therapies relating to editing the human gut microbiome, including a molecule linked to asthma in children.

Her institute is also assessing Crispr applications in agriculture, including tackling climate change by removing genes in the cow microbiome that are responsible for methane emissions.