The present invention provides FAHD1 for use in a method for the treatment or prevention of aberrations of the energy metabolism of the nervous system, pancreas, kidney, liver, muscles or adipose tissue. Further, a method of decarboxylating an organic compound is provided, which uses FAHD1 to decarboxylate the organic compound. Additionally, a method and a kit for identifying inhibitors of FAHD1 are provided.

Described herein are rats with a hepatic deficiency comprising decreased function, activity, or expression of an enzyme in the tyrosine catabolic pathway (such as fumarylacetoacetate hydrolase), and methods of using the same for in vivo engraftment and expansion of heterologous hepatocytes, such as human hepatocytes, analysis of human liver disease, and analysis of xenobiotics. Also disclosed is the use of immunodeficient rats for the engraftment and expansion of heterologous hepatocytes.

This disclosure provides vectors and strategies for increasing the efficiency of gene therapy in hepatocytes. The efficiency of the delivery of a corrected gene or wild type gene is improved through the use of delivery to hepatocytes via intrahepatic (parenchyma) administration or administration via the portal vein. In addition, the corrected gene or wild type gene is delivered using an isolated exogenous nucleic acid comprising a promoter that is specifically expressed in hepatocytes. These methods and isolated exogenous nucleic acids are useful to correct gene defects in the liver such as inherited diseases of the liver.

The present disclosure is in the field of methods and compositions for in vivo production of hepatocytes, such as human hepatocytes, as well as uses for the hepatocytes, including e.g., methods involving the administration of hepatocytes to a subject in need thereof, compositions that include such hepatocytes, and the like.

This disclosure provides vectors and strategies for increasing the efficiency of gene therapy in hepatocytes. The efficiency of the delivery of a corrected gene or wild type gene is improved through the use of delivery to hepatocytes via intrahepatic (parenchyma) administration or administration via the portal vein. In addition, the corrected gene or wild type gene is delivered using an isolated exogenous nucleic acid comprising a promoter that is specifically expressed in hepatocytes. These methods and isolated exogenous nucleic acids are useful to correct gene defects in the liver such as inherited diseases of the liver.

Described herein are rats with a hepatic deficiency comprising decreased function, activity, or expression of an enzyme in the tyrosine catabolic pathway (such as fumarylacetoacetate hydrolase), and methods of using the same for in vivo engraftment and expansion of heterologous hepatocytes, such as human hepatocytes, analysis of human liver disease, and analysis of xenobiotics. Also disclosed is the use of immunodeficient rats for the engraftment and expansion of heterologous hepatocytes.

Described herein are rats with a hepatic deficiency comprising decreased function, activity, or expression of an enzyme in the tyrosine catabolic pathway (such as fumarylacetoacetate hydrolase), and methods of using the same for in vivo engraftment and expansion of heterologous hepatocytes, such as human hepatocytes, analysis of human liver disease, and analysis of xenobiotics. Also disclosed is the use of immunodeficient rats for the engraftment and expansion of heterologous hepatocytes.

The present disclosure provides compositions and methods for gene therapy. Further, the present disclosure provides compositions and methods for treatment of HT1 through novel gene therapy mechanisms.

Presented herein are compositions and methods for improved gene editing with AAV vector constructs. Among other things, the present disclosure recognizes that homology arms of a certain length (e.g., at least 750 nt or at least 1000 nt each) may demonstrate improved editing activity. In some embodiments, the present disclosure recognizes that homology arms of a certain length (e.g., at least 750 nt or at least 1000 nt each) may demonstrate additional improvements in editing activity when homology arms are of different lengths.