Chemistry Nobel CRISPR Gene-editing Therapy: Novel Treatment for Chronic Pain

Recently, studies have proved that CRISPR-based gene silencing technology can alleviate chronic pain in mice. Although the therapy is still a long way from human use, scientists predict that it is a promising way to eliminate chronic pain that lasts for months or years.

In 2018, the World Health Organization (WHO) included chronic pain as an independent disease in its classification catalog for the first time. Chronic pain refers to pain that lasts or recurs for more than 3 months. The occurrence and development of chronic pain involve biological, psychological and social factors, since it can cause serious consequences such as sleep disturbance, lack of appetite, mental breakdown and even personality distortion and home violence. Many patients commit suicide because they cannot tolerate this long-term pain. Chronic pain is usually treated with opioids (such as morphine), which can lead to addiction, and thus the state has strictly controlled the use of such drugs, which further reduces the scope of patients' choices.

This dilemma inspired Ana Moreno and his colleagues at the University of California, San Diego to actively seek alternative treatments—CRISPR-based gene silencing technology.

Traditional CRISPR technology is to edit a person's genome as a treatment for blood diseases and certain genetic blindness. CRISPR, which treats chronic pain, does not directly edit genes, but it prevents gene expression, so it will not cause permanent changes.

When a stimulus triggers a neuron to send an electrical signal through a nerve in the spinal cord and upload it to the brain, pain will appear in the brain. When ion channels on a neuron open or close to allow ions to pass through, the ions conduct electrical current along the nerve. For chronic pain, part of this pathway becomes abnormally active. Although there are many types of ion channels, studies have shown that a sodium channel called Nav1.7 may play an important role in chronic pain. When the genetic code of this channel is mutated, people either experience extreme, constant pain, or feel no pain at all.

So Moreno and her team believe that preventing neurons from producing Nav1.7 can prevent pain signals from being transmitted to the brain. The team developed gene silencing therapy using CRISPR/Cas9, which won the Nobel Prize last year, and conducted experiments on mice. After implementing gene silencing therapy, they injected chemotherapy drugs or inflammatory agents to induce chronic pain. The results showed that these mice are more tolerant of painful stimuli. The results of the study were published on Science Translational Medicine on March 10, 2021.

In some cases in the experiment, pain relief can last up to 44 weeks after injection. More importantly, this therapy seems to reduce the expression of Nav1.7 without closing other sodium channels, and the mice did not lose any sensation other than pain, nor did they exhibit any side effects.

Although these preliminary results give people hope, it is not yet certain whether there will be the same pain relief effect in humans.

After 30 years of setbacks, gene therapy is currently developing rapidly and has become a key component of the treatment of various genetic and acquired diseases in humans. Gene therapy of inherited immune system diseases, hemophilia, eye and neurodegenerative diseases has brought great hope to mankind. Scientists and clinicians are engaged in basic, translational, and clinical research. With the support of the government and charity organizations, innovative or improved technologies will continue to emerge. Mankind can remain optimistic that gene therapy will become an important treatment for serious human diseases.