Rewriting the Code of Life, Witnessing Medical Miracles! CRISPR Technology Successfully Conquers Two Rare Diseases, Ushering in a New Era of Gene Therapy for Patients

Recently, CRISPR gene-editing technology has achieved significant progress in the field of rare disease treatment. Two patients of different age groups have successfully received treatment, bringing hope to millions of rare disease patients worldwide.

5-Month-Old Infant Becomes the World's First Beneficiary of CRISPR 2.0 Therapy

KJ Muldoon, a 5-month-old infant, was diagnosed with carbamoyl phosphate synthetase 1 deficiency (CPS1 deficiency) shortly after birth, with blood ammonia levels soaring to more than 30 times the normal value. The incidence of this disease is 1 in 1.3 million. A team from the Children's Hospital of Philadelphia developed a customized CRISPR 2.0 therapy for the infant, creating an adenosine base editor (K-abe) to target and repair the paternal gene mutation via mRNA nanoparticles. After three injections between February and April 2025, the infant's blood ammonia levels approached normal, and enzyme function was partially restored, marking the world's first successful case of in vivo personalized CRISPR 2.0 editing. The entire process from genetic diagnosis to treatment application took only 6 months, eliminating the need for liver transplantation and opening up a new path for rare disease treatment.

Photo: The infant who received gene-editing treatment with members of the research teamImage source: Children's Hospital of Philadelphia

18-Year-Old Adolescent Successfully Undergoes Prime Editing Treatment

An 18-year-old patient with chronic granulomatous disease, a rare immunodeficiency disorder, received Prime Editing treatment, a milestone in the CRISPR 3.0 era. Prime Medicine corrected the pathogenic gene mutation in a programmable manner to restore immune cell function. As reported in Nature on May 19, 2025, one month after treatment, the key enzyme function of two-thirds of the neutrophils in the patient's body was restored without serious side effects. This signifies the upgrade of CRISPR technology from "single-base correction" to "complex gene segment rewriting."

CRISPR Technology Iteration: Leading a New Era of Gene Therapy

CRISPR technology has undergone three major upgrades:

CRISPR 1.0 (Destructive Editing): The FDA-approved Cas9 technology in 2023 disrupts defective genes by cutting double-stranded DNA (e.g., for sickle cell disease). It requires in vitro editing of stem cells, involving complex processes and high costs.
CRISPR 2.0 (Single-Base Repair): Base editing technology achieves single-base substitution by combining nCas9 with deaminase. It enables in vivo administration for gene repair, suitable for diseases caused by single-base mutations (such as KJ Muldoon's treatment).
CRISPR 3.0 (Multi-Base Editing): Prime Editing supports single-base substitution, multi-base insertion/deletion, covering diseases with complex mutations (such as the 18-year-old patient's chronic granulomatous disease).

Challenges and Prospects of Technological Application

Current technical challenges include:

Efficacy Evaluation and Safety: The infant patient's efficacy relies on indirect indicators such as blood ammonia levels. The 18-year-old patient requires 6 months to 1 year of observation to assess edited cell survival. Long-term off-target effects and mosaicism need prolonged follow-up.
Delivery Efficiency and Cost: mRNA nanoparticles have insufficient targeting, limiting applications in organs like the brain and muscles. The cost of a single treatment exceeds 1 million US dollars, requiring standardized production to reduce expenses.
Ethical Norms: With the exploration of technologies such as prenatal editing, strict adherence to the "Regulations on the Administration of Human Genetic Resources" is necessary to balance technological innovation and ethics.

CRISPR technology is transforming medicine from "symptomatic control" to "genetic cure." Building on its foundational research advantages in CRISPR-Cas12a and other areas, China is expected to make breakthroughs in clinical translation and large-scale application, benefiting 400 million rare disease patients globally. From the gene-disrupting CRISPR 1.0 to the precision-repairing CRISPR 3.0, gene-editing technology has moved from the laboratory to the clinic in just a few years, turning the "impossible" into the "possible." KJ Muldoon's treatment journey confirms the boundless potential of science and reminds us that every technological breakthrough is built on the efforts of countless researchers and the hope of patients. In the future, as technology matures and global collaboration deepens, CRISPR may become another epoch-making tool in medical history, similar to antibiotics, making more "rare" diseases no longer "untreatable."

Review Expert

Professor Cheng BoranTaipei Zhongshan Hospital

Director of Obstetrics and Gynecology, Taipei Zhongshan Hospital
Professor, Chang Gung University
Current Positions:
Distinguished Attending Physician, Department of Obstetrics and Gynecology, Xiamen Chang Gung Hospital (Weijianwei-appointed "Professor Cheng Boran Famous Doctor Studio - Maternal-Fetal Medicine")
Chairman, Asia-Pacific Maternal-Fetal Medicine Foundation
President, Taiwan Women's Health Association
Fellow, International Society of Maternal-Fetal Medicine
Experience:
Tenured Professor, National Tsing Hua University
Founding Director of Obstetrics, Linkou Chang Gung Memorial Hospital
Founding Director of Genetic Medicine Center, Chang Gung Memorial Hospital
Founding President, Taiwan Maternal-Fetal Medicine Society
Former President, Taiwan Society of Medical Ultrasound
Fellow, World Association of Perinatal Medicine