Clinical trials advance as CRISPR takes off
The science of genome editing has advanced substantially in the past five years. The CRISPR/Cas9 genetic “scissors” technology, which secured the Nobel Prize in Chemistry in 2020 for Jennifer Doudna and Emmanuelle Charpentier, has more recently been complemented by next-generation tools like base, prime and epigenetic editing. David Liu of the Broad Institute said these new tools significantly increased the capabilities of genome editing, opening more possibilities for correcting genetic variants linked to disease with greater precision and efficacy.
Overall, there are over 130 clinical trials involving genome editing under way around the world and the first product based on CRISPR genome editing technology is now being submitted for approval to treat sickle cell disease and beta thalassemia. Victor Dzau of the U.S. National Academy of Medicine said the science had made remarkable strides in a few short years, with therapies under development for diseases ranging from blood disorders to sight loss and cancer.
Delivery and cost: twin challenges to equitable access
Despite the advances, however, the new science will not truly benefit humanity unless it is widely accessible, said Linda Partridge of Britain’s Royal Society. Sickle cell disease underscores the point: the condition affects millions of people worldwide, but most live in sub-Saharan Africa where healthcare capacity is severely limited. The first CRISPR editing therapies will therefore be out of reach for most of the global sickle cell community – a function of the expense and complexity of delivery, which involves invasive procedures to extract cells for editing, intensive chemotherapy and lengthy hospital stays. Emily Turner of the Bill & Melinda Gates Foundation said work needed to start now towards the “aspirational” goal of developing more convenient in vivo treatments that could meet the needs of patients in low- and middle-income countries.
If genome editing is to become the standard of care for the many diseases where it could theoretically work, addressing the pricing conundrum will be critical. There was recognition among scientists that scaling up delivery and reducing costs had to be done in a way that maintained the engagement of life science companies and their investors. In the last two years, six gene therapies have been dropped by commercial manufacturers for non-medical reasons. U.S. launch prices of $1 million to $3.5 million per patient proved too much for other countries. “People want to say ‘yes’ to gene therapies but they are going to struggle to do so,” said Steven Pearson, founder of the Institute for Clinical and Economic Review.
Public engagement key in controversial field
Right now, CRISPR is used in research almost exclusively for editing somatic cells, where changes will not be passed on to future generations. There is consensus that alterations to heritable cells leading to live births should remain out of bounds for the foreseeable future, with the result that research on embryos is limited. Robin Lovell-Badge of the Francis Crick Institute said any decision to eventually allow heritable genome editing would require a properly informed discussion across all stakeholders, and it would be contingent on demonstrating it could ever be done safely, which he said was “still a big if”. That public engagement is also unlikely to produce simple “yes/no” answers, requiring scientists to adapt to nuanced, conditional and evolving societal feedback.
China tightens oversight but critics still see gaps
While He Jiankui’s edited-babies experiment was already illegal under existing laws in 2018, China has accelerated the pace of biomedical regulation in the past five years. Yoajin Peng of the Chinese Academy of Sciences said there had been a slew of new laws and guidelines, with the latest measures on the ethical review of life science research issued on February 27, 2023. However, Joy Zhang of the University of Kent said China’s regulatory changes were “significant but not sufficient”. She expressed concern that governance measures were in practice still largely confined to academic institutions and failed to directly address how privately funded research was conducted in China.
Microbiome is next frontier for genome editing
Future applications of genome editing are set to expand beyond altering patient cells to changing the DNA of bacteria that live in the guts of humans and other animals – opening new avenues for fighting disease and even fighting climate change. CRISPR pioneer Jennifer Doudna of the Innovative Genomics Institute said this would lead to “a whole new area of biology”. Her team’s research is working to characterise and understand whole microbial communities. The aim is to develop microbial community editing technologies that will make it possible to target individual genomes, for example within the human gut. This approach opens the door to much wider therapeutic applications, since the microbiome is increasingly linked to all kinds of diseases, from infections and asthma to neurodegeneration. It could also revolutionise agriculture if a way is found to reduce methane generation in cow rumens, thereby cutting greenhouse gas emissions and converting animal feed to meat or milk efficiently.
Closing statement from the organising committee
The summit’s organising committee said in a closing statement that heritable human genome editing remained unacceptable “at this time”. It also called for an urgent global commitment to make treatments affordable and equitable.
