For the first time ever, researchers have tested on humans a precise gene editing technique, called base editing, as part of an experimental treatment aimed at keeping ‘bad’ blood cholesterol levels in check.
Developed by Boston-based Verve Technologies, the therapy reportedly resulted in up to 55 per cent drop in low-density lipoprotein (LDL) levels in trial participants. It did so by deactivating a gene – PCSK9 – in the liver that controls the levels of LDL – a major factor in heart disease.
While the findings reported by the company earlier this month raise the hope for developing safer gene therapies, they have also drawn criticism. There were two adverse events in the trial, including the death of one participant, but the company claims these were not related to the participants receiving the injection.
Verve’s CEO Sek Kathiresan clarified that both patients already had severely blocked arteries and suffered from heart problems after the infusion of the base editor. One died from cardiac arrest (unrelated to the infusion), while another participant did not disclose that he was suffering from chest pains prior to the trial.
The Science to control cholesterol by gene editing
The utilization of base editing is considered more precise and potentially safer compared to other gene-editing tools like CRISPR, as it modifies individual DNA bases without cutting the DNA strands. This process leads to controlled and targeted modifications, aiding in cholesterol control.
Dr Sayantan Ghosh, an analyst at Immuneel Therapeutics in Bengaluru, told Happiest Health that this method “deviates” from the conventional “cut and paste” method of CRISPR/Cas9 and “has more advantages over other gene editing technologies with few limitations.”
Think of base editing as changing words in a sentence, a small change compared to ripping a page out of a book and replacing it with a new and corrected one.
Base editing alters genetic information using modified Cas proteins (such as Cas9 or Cas12), which is an enzyme, and a guide RNA. The base editor is guided by RNA to a precise spot on the DNA molecule, enabling the swapping of one DNA base for another without breaking the strand of DNA.
The way forward
Prior to conducting trials on humans in the United Kingdom and New Zealand, Verve Technologies tested the therapy on monkeys. Apart from observing a 69% drop in LDL levels in the primates, the scientists also said the therapy did not cause any persistent liver or blood sugar issues.
Now, following the first human clinical trial, the Boston-based company states that it is moving forward with human trials in the US. It has obtained approval from the US Food and Drug Administration to enroll participants and assist them in controlling cholesterol.
While there is a need for further research and assessments to understand the safety and long-term implications of this innovative gene editing technique, Verve’s CEO Kathiresan envisions a future where such treatments become the norm.
Dr Ghosh states that base editing has successfully addressed other conditions, such as spinal muscular atrophy, by enhancing gene expression and compensating for the mutated gene. Furthermore, it exhibits potential in rendering T cells resistant to HIV infection, offering a promising strategy for HIV prevention.
“Although major advances have been made within base-editing technology so far, we have likely only scratched the surface of its potential in research and therapeutics,” says Dr Gosh.
