Related Experiment Video

Updated: Jan 18, 2026

CRISPR/Cas9-mediated Targeted Integration In Vivo Using a Homology-mediated End Joining-based Strategy
08:22

CRISPR/Cas9-mediated Targeted Integration In Vivo Using a Homology-mediated End Joining-based Strategy

Published on: March 12, 2018

15.5K

Advancing Gene Therapy for Phenylketonuria: From Precision Editing to Clinical Translation

Inseon Yu1, Jaemin Jeong1

  • 1Department of Biohealth Convergence, College of Science and Convergence Technology, Seoul Women's University, Seoul 01797, Republic of Korea.

International Journal of Molecular Sciences
|September 13, 2025
PubMed

Insights

Gene therapy offers new hope for phenylketonuria (PKU), an inherited disorder. Adenine base editing and viral gene transfer show promise in preclinical studies for treating PKU.

Area of Science:

  • Biochemistry
  • Genetics
  • Medical Genetics

Background:

  • Phenylketonuria (PKU) is an inherited metabolic disorder caused by phenylalanine hydroxylase (PAH) gene mutations.
  • Elevated phenylalanine (Phe) levels in the blood due to PAH deficiency can lead to severe neurological damage.
  • Current treatments, including low-Phe diets and tetrahydrobiopterin (BH4) therapy, have limitations and require lifelong adherence.

Purpose of the Study:

  • To review the pathophysiology of PKU and current treatment strategies.
  • To explore recent advancements in gene therapy for PKU, focusing on gene editing and viral-mediated gene delivery.
  • To discuss the translational challenges and future directions for gene therapy in PKU treatment.

Main Methods:

  • Review of preclinical and clinical studies on gene therapy for PKU.
  • Focus on adenine base editors (ABEs) and CRISPR-based gene editing systems.
  • Analysis of delivery methods including lipid nanoparticles (LNPs) and recombinant adeno-associated viruses (rAAV).

Main Results:

  • Gene editing technologies like ABEs and CRISPR show significant therapeutic potential in preclinical PKU models.
  • Viral-mediated gene transfer using rAAV vectors has demonstrated efficacy in delivering therapeutic genes.
  • Lipid nanoparticles (LNPs) are emerging as effective delivery vehicles for gene-editing components.

Conclusions:

  • Gene therapy, particularly adenine base editing and rAAV-mediated gene transfer, represents a promising therapeutic avenue for PKU.
  • Overcoming translational challenges related to delivery, safety, and long-term efficacy is crucial for clinical application.
  • Further research and development are needed to ensure the safety and effectiveness of gene therapies for widespread PKU treatment.

Keywords:
Phenylketonuria (PKU)adeno-associated virusanimal modelbase editinggene therapy

More Related Videos

Lentiviral Vector-mediated Gene Therapy of Hepatocytes Ex Vivo for Autologous Transplantation in Swine09:54

Lentiviral Vector-mediated Gene Therapy of Hepatocytes Ex Vivo for Autologous Transplantation in Swine

Published on: November 4, 2018

8.5K
In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing10:44

In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing

Published on: May 5, 2023

1.8K

Related Concept Videos

Gene Therapy00:59

Gene Therapy

Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be...
27.3K
What is Genetic Engineering?00:49

What is Genetic Engineering?

Overview
79.6K
In-vitro Mutagenesis01:16

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
16.0K
CRISPR01:59

CRISPR

Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced...
57.5K
Microorganisms in Medicine and Therapeutics01:29

Microorganisms in Medicine and Therapeutics

Microorganisms play a fundamental role in vaccine development, gene therapy, and therapeutic production. Their biological properties are harnessed to advance medicine and public health. Beyond immunization, microorganisms contribute to gut health, antibiotic synthesis, and genetic disease treatment.Live Attenuated and Inactivated VaccinesLive attenuated vaccines, such as the measles, mumps, and rubella (MMR) vaccine, utilize weakened forms of pathogens to closely resemble natural infections.
987
Inborn Errors of Metabolism01:20

Inborn Errors of Metabolism

Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake...
697