Gene therapy and genome editing are very promising molecular medicine approaches that aim to provide long-term correction of human disease-causing mutations. Gene therapy, by gene replacement, relies on the use of exogenous DNA as a drug product. As such, gene therapy introduces a correct copy of the endogenous gene affected by mutations in the target cell. In this approach, tissue-specific promoters control the transcription of the therapeutic gene. However, the application of this approach in a growing liver is still limited by concerns about the long-term safety and efficacy of the therapy. Moreover, the re-administration of the therapeutic gene is discouraged by the generation of neutralizing antibodies generated after the first administration.
The recent progress of genome editing technologies, such as CRISPR/Cas9 platform, enable the specific and permanent modification of the genome in the cell or living organism. This strategy allows the insertion, deletion or replacement of DNA in a specific site in the genome. Therefore, the modification of the DNA is stably transmitted to daughter cells upon duplication. This site-specific correction of disease-causing mutations provides new therapeutic avenues to treat and cure human diseases. Although the approach shows efficacy in animal models, its broad translation to the clinic needs further improvements and investigations to limit its undesired off-target activity, to reduce the viral doses used and control the expression of the therapeutic endonuclease.
Inborn errors of liver metabolism are a heterogeneous set of genetic human disorders characterized by defective proteins involved in the synthesis or catabolism of amino acids, lipids or carbohydrates. Likewise, they provoke a number of metabolic conditions that result in several degrees of human complaint. Overall, the global prevalence of inborn errors of liver metabolism accounts for a significant proportion of childhood illnesses, representing about 10% of pediatric liver transplants.
Since the disease is caused by the modification of a single gene, inborn errors of liver metabolism are an attractive class of diseases that can be potentially treated by gene editing and therapy technologies.
This Research Topic focuses on articles - including reviews, opinions, original research among others - to explore the therapeutic potential of gene editing and therapy technologies to treat and cure inborn errors of liver metabolism. We welcome manuscripts related to, but not limited to, the following:
• Use of new in vitro and in vivo animal models for liver metabolic diseases treated with gene therapy or genome editing approaches
• Safety and efficacy of gene therapy or genome editing (integration studies, off-target activity, high-fidelity endonucleases)
• Strategies to improve gene therapy or genome editing approaches (innovative vectors, mRNA/protein delivery of nucleases or therapeutic genes, lipid nanoparticles)
• Strategies enabling re-administration of therapeutic gene (immunomodulation)
• Immunological aspects of gene therapy and genome editing approaches
• Investigations on transgene persistence, correlation between liver maturation and efficacy of the therapy
Gene therapy and genome editing are very promising molecular medicine approaches that aim to provide long-term correction of human disease-causing mutations. Gene therapy, by gene replacement, relies on the use of exogenous DNA as a drug product. As such, gene therapy introduces a correct copy of the endogenous gene affected by mutations in the target cell. In this approach, tissue-specific promoters control the transcription of the therapeutic gene. However, the application of this approach in a growing liver is still limited by concerns about the long-term safety and efficacy of the therapy. Moreover, the re-administration of the therapeutic gene is discouraged by the generation of neutralizing antibodies generated after the first administration.
The recent progress of genome editing technologies, such as CRISPR/Cas9 platform, enable the specific and permanent modification of the genome in the cell or living organism. This strategy allows the insertion, deletion or replacement of DNA in a specific site in the genome. Therefore, the modification of the DNA is stably transmitted to daughter cells upon duplication. This site-specific correction of disease-causing mutations provides new therapeutic avenues to treat and cure human diseases. Although the approach shows efficacy in animal models, its broad translation to the clinic needs further improvements and investigations to limit its undesired off-target activity, to reduce the viral doses used and control the expression of the therapeutic endonuclease.
Inborn errors of liver metabolism are a heterogeneous set of genetic human disorders characterized by defective proteins involved in the synthesis or catabolism of amino acids, lipids or carbohydrates. Likewise, they provoke a number of metabolic conditions that result in several degrees of human complaint. Overall, the global prevalence of inborn errors of liver metabolism accounts for a significant proportion of childhood illnesses, representing about 10% of pediatric liver transplants.
Since the disease is caused by the modification of a single gene, inborn errors of liver metabolism are an attractive class of diseases that can be potentially treated by gene editing and therapy technologies.
This Research Topic focuses on articles - including reviews, opinions, original research among others - to explore the therapeutic potential of gene editing and therapy technologies to treat and cure inborn errors of liver metabolism. We welcome manuscripts related to, but not limited to, the following:
• Use of new in vitro and in vivo animal models for liver metabolic diseases treated with gene therapy or genome editing approaches
• Safety and efficacy of gene therapy or genome editing (integration studies, off-target activity, high-fidelity endonucleases)
• Strategies to improve gene therapy or genome editing approaches (innovative vectors, mRNA/protein delivery of nucleases or therapeutic genes, lipid nanoparticles)
• Strategies enabling re-administration of therapeutic gene (immunomodulation)
• Immunological aspects of gene therapy and genome editing approaches
• Investigations on transgene persistence, correlation between liver maturation and efficacy of the therapy
