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From Lab to Life: CRISPR's Advancements in Personalized Therapies for Metabolic, Blood, and Other Disorders

From Lab to Life: CRISPR's Advancements in Personalized Therapies for Metabolic, Blood, and Other Disorders

By Clement Dionglay

May 28, 2025

CRISPR gene editing is a revolutionary technology that allows scientists to make precise and targeted changes to the DNA of living organisms. It is often likened to a "molecular word processor" for DNA, enabling researchers to "cut," "paste," or "rewrite" specific genetic sequences. The technology has a wide range of applications in agriculture, bioinformatics, and health and medicine. In agriculture, gene editing technology has been used by researchers to enhance crop yield, improve nutritional content, and increase crop resistance to diseases and abiotic stresses. It is also being used in improving livestock traits.

In the past three years, researchers have used CRISPR gene editing technology to develop gene therapies for various health conditions. Examples of these conditions include phenylketonuria, a rare inherited disorder that causes the amino acid phenylalanine to accumulate in the body; inherited blood disorders such as beta-thalassemia and sickle cell disease; and the rare blood disorder hemophilia. Researchers have also developed an antidote for mushroom poisoning and a treatment for antimicrobial resistance using gene editing. A recent breakthrough in personalized gene editing involves the successful use of CRISPR-based gene therapy tailored for an infant with a rare, life-threatening metabolic disorder developed by scientists in the United States.

Carbamoyl Phosphate Synthetase 1 (CPS1) Deficiency

In May 2025, a team at the Children's Hospital of Philadelphia (CHOP) and Penn Medicine announced the first known case of a personalized CRISPR-based medicine administered to a single patient. The infant, KJ, diagnosed with severe carbamoyl phosphate synthetase 1 (CPS1) deficiency, received a customized gene-editing therapy designed to correct a specific gene mutation in his liver cells. This treatment, delivered via lipid nanoparticles, has shown positive results, allowing the baby to tolerate increased protein in his diet and require less medication.

Pediatric geneticist and Director of CHOP’s Gene Therapy for Inherited Metabolic Disorders Program Rebecca Ahrens-Nicklas, MD, PhD, and Kiran Musunuru, MD, PhD, MPH, ML, MRA, a cardiologist, geneticist, and gene editor at Penn, created a base-editing therapy that corrects one of KJ's two copies of the CPS1 gene. After the treatment received approval from the U.S. Food and Drug Administration (FDA), KJ was given a low dose of the treatment in February 2025 when he was six months old, followed by larger doses in March and April. He has not shown any serious side effects and is now able to eat more protein than before.

This achievement highlights the potential to rapidly develop and deploy individualized gene-editing treatments for other rare genetic diseases, offering hope for conditions that previously had limited or no treatment options. The process, from diagnosis to treatment, took only six months, demonstrating the increasing speed and precision of personalized gene editing.

Phenylketonuria

Phenylketonuria (PKU) is a genetic disorder that occurs in newborns, causing the amino acid phenylalanine to accumulate in the bloodstream. The impacts of uncontrolled PKU include intellectual disability, seizures, and psychiatric issues. There are current therapies that help with this disease, but patients need to observe meticulous, lifelong compliance.

To help with this disorder, a team of researchers from the Perelman School of Medicine explored CRISPR gene editing techniques that can be used for potential PKU treatments. They studied a prime editing approach that may correct the PAH c.1222C>T genetic variant that causes the condition. The team experimented on mouse liver and human liver cells and proved the effectiveness of the method. In another study, the research team used base editing for PKU treatment, which showed phenylalanine levels returning to normal within 48 hours.

In a separate research in China, scientists from Jiangsu Academy of Agricultural Sciences and Yangzhou University developed low glutelin rice using the CRISPR-Cas9 gene editing system. Rice with low glutelin content will help patients with PKU and chronic kidney disease.

Sickle Cell Disease

Sickle cell disease (SCD) is a group of inherited blood disorders affecting approximately 100,000 people in the U.S. It is most common in African Americans and, while less prevalent, also affects Hispanic Americans. In December 2023, the United States Food and Drug Administration (FDA) approved Casgevy and Lyfgenia, the first cell-based gene therapies to treat SCD. Casgevy is the first FDA-approved treatment developed using CRISPR-Cas9 genome editing technology, signaling an innovative advancement in gene therapy.

Casgevy is a groundbreaking cell-based gene therapy that has received approval to treat SCD in patients aged 12 years and older who experience recurrent vaso-occlusive crises (VOCs). It is notable as the first FDA-approved therapy to utilize CRISPR-Cas9 gene editing technology. Casgevy has previously received approval in the United Kingdom in November 2023.

Lyfgenia is a cell-based gene therapy for patients aged 12 years and older with SCD who have a history of vaso-occlusive events. Unlike Casgevy, which uses CRISPR-Cas9 to reactivate fetal hemoglobin production, Lyfgenia employs a lentiviral vector as a gene delivery vehicle.

Other Treatments Developed Using Gene Editing Techniques

Scientists in China have discovered a potential antidote for death cap mushroom poisoning, which causes 90% of mushroom-related deaths. Using CRISPR-Cas9 technology, they identified that the STT3B enzyme is crucial for the toxin alpha-amanitin to enter and damage cells. By screening compounds that block STT3B, they found indocyanine green, a dye developed for photography that is currently being used for medical imaging. In mice, this treatment reduced the mortality rate from alpha-amanitin poisoning from 90% to 50%.

At the ECMID Global Congress, Dr. Rodrigo Ibarra-Chávez from the University of Copenhagen, Denmark, highlighted the use of CRISPR technology as an innovative tool to combat the growing global crisis of antimicrobial resistance (AMR). His team is developing guided CRISPR systems to directly target and attack AMR genes in bacteria, aiming to both treat infections and prevent the spread of resistance. To overcome bacterial defense mechanisms against CRISPR, they are also exploring the use of anti-CRISPRs and defense inhibitors. Their research, initially focused on Staphylococcus aureus and Escherichia coli, now includes work on Streptococci necrotizing soft tissue infections in collaboration with other professors.

Future Treatments

Kyoto University researchers used gene editing to restore dystrophin protein function in stem cells derived from Duchenne muscular dystrophy (DMD) patients, offering a promising therapeutic approach. DMD is a severe, incurable muscle degeneration disorder caused by mutations in the dystrophin gene. The scientists used a dual CRISPR-Cas3 system to remove large, damaged sections of the dystrophin gene, allowing cells to produce functional dystrophin protein. This method could potentially lead to future gene therapies for DMD and similar genetic disorders, pending safe and efficient delivery to muscle tissues.

The Wisconsin Institute for Discovery, backed by the US National Institutes of Health, is working on a project to develop CRISPR gene editing therapies for two diseases that can cause blindness: Leber Congenital Amaurosis (LCA) and Best Disease (BD). Researchers will combine advanced CRISPR technology with novel drug delivery methods to treat these currently untreatable hereditary conditions, aiming to gain a comprehensive understanding of the efficacy of their gene editing treatment. LCA severely affects children's vision, while BD causes slow central vision loss in older individuals.

Conclusion

The future of personalized gene editing therapies is rapidly evolving and exceptionally promising as it moves from theoretical concepts to clinical reality. Recent breakthroughs, such as the personalized CRISPR-based treatment for an infant with a CPS1 deficiency, underscore the accelerating pace of this field. Advancements are expected in more therapeutic and delivery methods, while offering hope to millions with previously untreatable diseases. While challenges remain, the rapid pace of innovation suggests a future where highly customized, precise, and potentially curative genetic interventions become a more common reality.

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