Unknown

Dataset Information

0

Restoring Ureagenesis in Hepatocytes by CRISPR/Cas9-mediated Genomic Addition to Arginase-deficient Induced Pluripotent Stem Cells.


ABSTRACT: Urea cycle disorders are incurable enzymopathies that affect nitrogen metabolism and typically lead to hyperammonemia. Arginase deficiency results from a mutation in Arg1, the enzyme regulating the final step of ureagenesis and typically results in developmental disabilities, seizures, spastic diplegia, and sometimes death. Current medical treatments for urea cycle disorders are only marginally effective, and for proximal disorders, liver transplantation is effective but limited by graft availability. Advances in human induced pluripotent stem cell research has allowed for the genetic modification of stem cells for potential cellular replacement therapies. In this study, we demonstrate a universally-applicable CRISPR/Cas9-based strategy utilizing exon 1 of the hypoxanthine-guanine phosphoribosyltransferase locus to genetically modify and restore arginase activity, and thus ureagenesis, in genetically distinct patient-specific human induced pluripotent stem cells and hepatocyte-like derivatives. Successful strategies restoring gene function in patient-specific human induced pluripotent stem cells may advance applications of genetically modified cell therapy to treat urea cycle and other inborn errors of metabolism.

SUBMITTER: Lee PC 

PROVIDER: S-EPMC5155330 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

Restoring Ureagenesis in Hepatocytes by CRISPR/Cas9-mediated Genomic Addition to Arginase-deficient Induced Pluripotent Stem Cells.

Lee Patrick C PC   Truong Brian B   Vega-Crespo Agustin A   Gilmore W Blake WB   Hermann Kip K   Angarita Stephanie Ak SA   Tang Jonathan K JK   Chang Katherine M KM   Wininger Austin E AE   Lam Alex K AK   Schoenberg Benjamen E BE   Cederbaum Stephen D SD   Pyle April D AD   Byrne James A JA   Lipshutz Gerald S GS  

Molecular therapy. Nucleic acids 20161129 11


Urea cycle disorders are incurable enzymopathies that affect nitrogen metabolism and typically lead to hyperammonemia. Arginase deficiency results from a mutation in Arg1, the enzyme regulating the final step of ureagenesis and typically results in developmental disabilities, seizures, spastic diplegia, and sometimes death. Current medical treatments for urea cycle disorders are only marginally effective, and for proximal disorders, liver transplantation is effective but limited by graft availab  ...[more]

Similar Datasets

| S-EPMC8686786 | biostudies-literature
| S-EPMC7192158 | biostudies-literature
| S-EPMC4850082 | biostudies-literature
| S-EPMC6298866 | biostudies-literature
| S-EPMC3813848 | biostudies-other
| S-EPMC5481315 | biostudies-other
| S-EPMC6167567 | biostudies-literature
| S-EPMC6704636 | biostudies-literature
| S-EPMC4586837 | biostudies-other
| S-EPMC9490201 | biostudies-literature