Sequences of a serotype 8 adeno-associated virus and vectors and host cells containing these sequences are provided. Also described are methods of using such host cells and vectors in production of rAAV particles.

The present invention provides, among other things, methods of treating ornithine transcarbamylase deficiency, including administering to a subject in need of treatment a composition comprising an mRNA encoding an ornithine transcarbamylase protein at a low dose and at an administration interval such that at least one symptom or feature of the OTC deficiency is reduced.

Viral vectors comprising engineered hOTC DNA and RNA sequences are provided which when delivered to a subject in need thereof are useful for treating hyperammonemia, ornithine transcarbamylase transcarbamylase deficiency and symptoms associated therewith. Also provided are methods of using hOTC for treatment of liver fibrosis cirrhosis in OTCD patients by administering hOTC.

Non-viral delivery systems comprising engineered hOTC DNA and RNA sequences are provided which when delivered to a subject in need thereof are useful for treating hyperammonemia, ornithine transcarbamylase transcarbamylase deficiency and symptoms associated therewith. Also provided are methods of using hOTC for treatment of liver fibrosis and/or cirrhosis in OTCD patients by administering hOTC.

The present invention relates to a recombinant microorganism capable of producing putrescine, in which the microorganism is modified to have enhanced NCgl2522 activity, thereby producing putrescine in a high yield, and a method for producing putrescine using the microorganism.

The present disclosure describes compositions and methods for treating ornithine transcarbamylase (OTC) deficiency. The compositions include a lipid formulation and messenger RNA (mRNA) encoding an OTC enzyme. The lipid formulations can comprise an ionizable cationic lipid in a lipid nanoparticle encapsulating the mRNA.

The present invention provides, among other things, methods of treating ornithine transcarbamylase deficiency, including administering to a subject in need of treatment a composition comprising an mRNA encoding an ornithine transcarbamylase protein at a low dose and at an administration interval such that at least one symptom or feature of the OTC deficiency is reduced.

Disclosed herein are novel compounds, pharmaceutical compositions comprising such compounds and related methods of their use. The compounds described herein are useful, e.g., as liposomal delivery vehicles to facilitate the delivery of encapsulated polynucleotides to target cells and subsequent transfection of said target cells, and in certain embodiments are characterized as having one or more properties that afford such compounds advantages relative to other similarly classified lipids.

A dual vector system for treating ornithine transcarbamylase deficiency is provided. The system includes ((a) a gene editing AAV comprising a first AAV rh79 capsid and a first vector genome comprising a 5 ITR, a sequence encoding a meganuclease that targets PCSK9 under control of regulatory sequences that direct expression of the meganuclease in a target cell comprising a PCSK9 gene, and a 3 ITR; and (b) a donor AAV vector comprising a second AAV capsid and a second AAV rh79 vector genome comprising: a 5ITR, a 5 homology directed recombination (HDR) arm, a transgene encoding ornithine transcarbamylase (OTC) and regulatory sequences that direct expression of the transgene in the target cell, a 3 HDR arm, and a 3 ITR.

A microorganism produces guanidinoacetic acid (GAA) and has at least one gene coding for a protein having the function of a NADH-dependent dehydrogenase. A method for the fermentative production of GAA uses such microorganism. A method produces creatine through fermentative production. Industrial feed stocks are used as starting material in the fermentative process.