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Gene therapy for genetic diseases using CRISPR is aimed not only at reducing symptoms, but at changing the molecular cause of the disease. The name CRISPR is also pronounced as “crisper.” The technology allows finding a specific DNA sequence, turning off a pathological gene, restoring its function, or changing the regulation of another gene.

In pediatrics, this approach is important for hereditary diseases that damage the brain, liver, hematopoietic system, muscles, or visual organs from the earliest years of life. Its application depends on an accurate diagnosis, type of mutation, availability of target cells, and clinical evidence.

How CRISPR works in pediatric gene therapy

To understand how the system works, it can be imagined as a programmable molecular tool. The guide RNA recognizes the target DNA sequence, and the Cas9 protein or another editor performs a change at the specified point. After that, the cell repairs the DNA, and this process is used for therapeutic effect.

The main types of editing differ by the type of change:

• turning off a gene whose activity causes disease;
• correcting a single pathological DNA “letter” by base editing;
• removing the defective genome segment;
• restoring synthesis of the required protein by changing a regulatory sequence;
• introducing useful genetic information with more precise next-generation editors;

The choice of strategy is determined by the specific mutation and tissue biology. One diagnosis may require different editors in different children.

Forms of CRISPR therapy administration

Clinical modes of administration are divided into editing outside the body and directly inside the body. Changes are made to somatic cells, so they should not be passed on to future generations. WHO distinguishes somatic from hereditary genome editing, each subject to different levels of control.

1. Ex vivo – cells are taken from the child, edited in the laboratory, tested, and returned intravenously.
2. In vivo – editor components are delivered to the target organ via lipid nanoparticles or viral vectors.
3. Local administration – the drug is delivered to a specific tissue, for example under the retina of the eye.
4. Personalized editing – an editor is created for a unique mutation of one child or a small group of patients.

Ex vivo allows testing cells before administration, but requires complex manufacturing and often preparatory chemotherapy. In vivo simplifies access to the liver and certain tissues but increases demands on delivery accuracy.

Genetic diseases for which CRISPR is already used

The greatest clinical data accumulation is for hereditary blood diseases. Casgevy uses CRISPR/Cas9 to edit a patient’s own hematopoietic stem cells to increase fetal hemoglobin synthesis. This reduces sickle-shaped erythrocyte deformation and can eliminate the need for regular transfusions in transfusion-dependent beta-thalassemia.

As of July 1, 2026, the FDA expanded Casgevy’s indication in the USA to children from 2 years old with recurrent vaso-occlusive crises or transfusion-dependent beta-thalassemia. In the European Union, EMA indications remain for patients from 12 years old who are eligible for hematopoietic stem cell transplantation and have no suitable familial donor.

FDA pediatric results provide specific guidelines:

• all 8 evaluated children with sickle cell disease had no severe crises for at least 12 consecutive months;
• 8 out of 9 evaluated children with beta-thalassemia achieved transfusion independence for 12 consecutive months;
• median confirmed transfusion independence was 20.1 months;
• approval for ages 2-4 was partly based on extrapolation of data from older children;

These figures apply to small groups and do not guarantee identical results for every child. Duration of effect and long-term safety continue to be evaluated.

Personalized CRISPR Therapy for Rare Mutations

In 2025, a team from CHOP and the University of Pennsylvania reported the first systemic personalized base editing for an infant with severe CPS1 deficiency. The disease disrupts ammonia utilization and can quickly cause brain damage. The child received the first dose at 6-7 months of age, after which they were able to consume more protein and reduce the dose of nitrogen excretion medication. No serious adverse events were recorded in initial observations, but long-term monitoring is required.

This case demonstrates an “N-of-1” model, where therapy is designed for a single mutation. It does not prove universal efficacy but shows the possibility of adapting the platform to ultra-rare diseases.

Risks, Limitations, and Safety Monitoring

CRISPR is not a standard solution for all hereditary diagnoses. The risk depends on the editor, delivery method, target organ, child’s age, and preparatory treatment.

Before therapy, the team assesses the following factors:

1. Confirmation of the pathogenic mutation and its association with disease manifestations.
2. The ability to deliver the editor to a sufficient number of required cells.
3. The likelihood of off-target DNA changes.
4. The risk of incomplete or heterogeneous editing of cells.
5. Toxicity of preparatory chemotherapy, immune reactions, and infection risk.
6. Availability of alternatives – drug therapy, transplantation, or other gene therapy.

For Casgevy, the FDA notes mucositis, febrile neutropenia, decreased appetite, delayed platelet engraftment, hypersensitivity reactions, and off-target editing risks. Complete myeloablative conditioning is performed before administration, so treatment is only possible in specialized centers.

Due to the possibility of delayed effects, the FDA recommends up to 15 years of monitoring for genome editing products. This is necessary to control the stability of the effect, off-target changes, and late complications.

How a Child is Referred for CRISPR Therapy Evaluation

The pathway starts with molecular confirmation of the diagnosis. The family needs a center experienced in pediatric genetics, the relevant disease, transplantation, or gene therapy.

The practical sequence of actions looks like this:

• gather the genetic report with accurate gene and variant notation;
• obtain evaluation from a pediatric geneticist and relevant specialist;
• determine whether an approved therapy, early access program, or clinical trial exists;
• check criteria for age, severity, organ function, and prior treatment;
• discuss expected effect, uncertainties, hospitalization, and long-term monitoring;
• obtain independent information about alternative treatment methods;

The decision is made by a multidisciplinary team together with the parents or legal representatives. Participation in a study does not guarantee benefit, and offers of “CRISPR treatment” outside of regulatory-controlled centers require verification.