Prime Medicine doses first patient with in-body prime editing therapy PM577a for Wilson disease

U.S. company Prime Medicine said on the 5th that it had administered the gene-editing therapy PM577a to a patient with Wilson disease, a rare genetic disorder, biz.chosun.com reports. It is the first clinical trial to deliver a prime editing tool directly into the human body. A global phase 1/2 trial is underway, and initial results are expected next year biz.chosun.combiz.chosun.combiz.chosun.comOpen source ↗.

Wilson disease is estimated to affect about 1 in 30,000 people. The body cannot properly excrete accumulated copper because of mutations in the ATP7B gene, which encodes a liver-cell protein that moves excess copper into bile. The location and type of mutation vary by patient biz.chosun.combiz.chosun.combiz.chosun.comOpen source ↗.

Current treatment relies on drugs that bind copper to help excrete it, or on zinc preparations that block copper absorption in the intestine. Most patients must take medication for life, and severe liver failure may require a liver transplant. The researchers consider that editing could correct the cause of the disease directly biz.chosun.combiz.chosun.combiz.chosun.comOpen source ↗.

How prime editing works

Prime editing was published by the Broad Institute in the journal Nature in 2019. It is considered an advance over CRISPR-Cas9, which cuts both DNA strands and relies on the cell's repair function. During that repair, unwanted sequences can be inserted or deleted biz.chosun.combiz.chosun.combiz.chosun.comOpen source ↗.

Prime editing cuts only one of the two strands. An enzyme that writes new genetic information works together with a guide RNA that marks where and what to correct. The method can substitute among the four bases (A, T, G, C) and insert or delete short sequences biz.chosun.combiz.chosun.combiz.chosun.comOpen source ↗.

Delivery and trial design

The editing tool is packed into lipid nanoparticles, the delivery technology also used in COVID-19 mRNA vaccines, and given intravenously. The particles are designed to reach liver cells. The company aims for a durable effect from a single dose biz.chosun.combiz.chosun.combiz.chosun.comOpen source ↗.

PM577a targets the H1069Q mutation. According to the company, it accounts for about 30% to 50% of ATP7B mutations causing Wilson disease in the United States and Europe. A follow-up therapy for R778L, common in East Asia, is in preclinical development biz.chosun.combiz.chosun.combiz.chosun.comOpen source ↗.

The FDA-approved gene-editing therapy Casgevy edits a patient's stem cells in the lab (ex vivo) before reinfusion. Editing inside the body removes cell collection and processing, which can reduce treatment time and manufacturing cost. It requires precise delivery to the target organ and minimal changes to non-target DNA, and long-term effects of persistent changes must be examined biz.chosun.combiz.chosun.combiz.chosun.comOpen source ↗.

The trial enrolls adults whose symptoms are stabilized with medication. It will assess safety and dosage, whether copper excretion is restored, and whether patients can stop existing drugs biz.chosun.combiz.chosun.combiz.chosun.comOpen source ↗.