The present disclosure is directed to compositions and methods for the treatment of Metabolic Liver Disorders. The compositions and methods can comprise an adeno-associated virus (AAV) piggyBac polynucleotide comprising a transgene. The transgene may comprise ornithine transcarbamylase (OTC) or methylmalonyl-CoA mutase (MUT1).

Provided is a polymer comprising a hydrolysable polymer backbone, the polymer backbone comprising (i) monomer units comprising a hydrophobic side chain; and (ii) monomer units comprising a cationic side chain; wherein the cationic side chain comprises a polyamine with at least one tertiary amine and only a single nucleophilic center, optionally at the terminus of the polyamine, as well as a method of preparing said polymer, and a method of delivering a nucleic acid and/or polypeptide to a cell using the polymer.

The invention relates to a method of reacting one or more L-nucleotides with a first L-nucleic acid in the presence of a D-enzyme that adds the one or more L-nucleotides to the 3′ end of the first L-nucleic acid.

The present disclosure relates to methods, compositions, and kits for generating a library of tagged nucleic acid fragments without using PCR amplification, including methods and compositions for fragmenting and tagging nucleic acids (e.g., DNA) using transposome complexes immobilized on solid support.

The present invention refers to hyperactive variants of a transposase of the transposon system Sleeping Beauty (SB). The invention further refers to corresponding nucleic acids producing these variants, to a gene transfer system for stably introducing nucleic acid(s) into the DNA of a cell by using these hyperactive variants of a transposase of the transposon system Sleeping Beauty (SB) and to transposons used in the inventive gene transfer system, comprising a nucleic acid sequence with flanking repeats (IRs and/or RSDs). Furthermore, applications of these transposase variants, the transposon, or the gene transfer system are also disclosed such as gene therapy, insertional mutagenesis, gene discovery (including genome mapping), mobilization of genes, library screening, or functional analysis of genomes in vivo and in vitro. Finally, pharmaceutical compositions and kits are also encompassed.

The present disclosure provides, among other things, novel cyclic-GMP-AMP (cGAMP) analogs, mimics, mimetics and variants, and compositions and kits thereof; methods of using the compounds as described herein for treating cancer, and immune disease, disorders, or conditions; methods of using the compounds as described herein for modulating cGAS and STING; and methods of designing or characterizing a cGAS modulator.

Disclosed are genetic delivery systems that utilize genetic elements of the piggyBac family transposon system, and methods of introducing nucleic acid into target cells using the genetic delivery systems.

Gene therapy compositions and methods are provided for targeting a very low-density lipoprotein receptor gene (VLDLR) and a low-density lipoprotein receptor gene (LDLR) to lower total cholesterol and/or low-density lipoprotein cholesterol (LDL-C) in a patient, thereby treating or mitigating familial hypercholesterolemia.

A chimeric molecule of one or more proteins or peptides fused, complexed or linked to one or more anionic molecules. Efficient in vitro and in vivo delivery is attained by encapsulating these molecules in cationic lipids or cationic liposomes. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.

Provided herein, among other things, is a conjugate comprising a polymerase and a nucleoside triphosphate, where the polymerase and the nucleoside triphosphate are covalently linked via a linker that comprises a cleavable linkage. A set of such conjugates, where the conjugates correspond to G, A, T (or U) and C is also provided. Methods for synthesizing a nucleic acid of a defined sequence are also provided. The conjugates can also be used for sequencing applications.