The present invention provides methods of generating a recombinant AAV vector with reduced immunogenicity, comprising: providing eukaryotic cells with a nucleic acid comprising a sequence of interest that is flanked by AAV inverted terminal repeats, wherein the nucleic acid comprises CpG dinucleotide sites, wherein at least a portion of the CpG dinucleotide sites are methylated, wherein the eukaryotic cell expresses one or more other components necessary to achieve recombinant AAV biosynthesis, whereby the recombinant AAV vector is generated by the eukaryotic cell, wherein the generated recombinant AAV vector comprises nucleic acid wherein at least a portion of the CpG dinucleotide sites are methylated.

The invention relates to an adeno-associated virus (AAV) vector comprising a nucleic acid construct for the expression of a glucose-6-phosphatase-a (G6Pase-a) in a cell, the construct comprising a nucleic acid sequence encoding the G6Pase-a, wherein the nucleic acid sequence encoding the G6Pase-a is operably linked to a human alpha-1 antitrypsin (hAAT) promoter, a cell transformed with the vector of the invention, a composition comprising the vector or the cell of the invention, and the use thereof.

The present disclosure relates to the field of molecular biology and more specifically to methods for detecting anti-carbamylated protein (anti-CarP) antibodies in the serum of rheumatoid arthritis (RA) patients.

Disclosed herein are compositions and methods for modulatimi the production of a protein in a target cell, The compositions and methods disclosed herein are capable of ameliorating diseases associated with protein or enzyme deficiencies.

The invention relates to MIC-1 fusion proteins. More specifically it relates to compounds comprising fusion proteins comprising a MIC-1 protein or an analogue thereof at the C-terminus of the fusion protein and a functional variant of human A1AT (A1AT) at the N-terminus of the fusion protein connected via a peptide linker. The compounds of the invention have MIC-1 activity. The invention also relates to pharmaceutical compositions comprising such compounds and pharmaceutically acceptable excipients, as well as the medical use of the compounds.

Transgenic non-human animals, e.g., rodents, e.g., mice comprising genomic mutations that inactive all of the serpinlA genes and thus lack any functional serpinA1 genes. As a result of the genomic mutations, the animals express no hepatic or circulatory AAT protein. Also provided herein are cells and tissues derived from the transgenic mice.

Disclosed herein are methods for decreasing A1AT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of fibrosis. Disclosed herein are methods for decreasing A1AT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of liver disease, such as, A1ATD associated liver disease, and pulmonary disease, such as, A1ATD associated pulmonary disease in an individual in need thereof. Methods for inhibiting A1AT mRNA and protein expression can also be used as a prophylactic treatment to prevent individuals at risk for developing a liver disease, such as, A1ATD associated liver disease and pulmonary disease, such as, A1ATD associated pulmonary disease.

The invention relates to isolated nucleic acids and rAAV-based compositions, methods and kits useful for treating genetic diseases (e.g., alpha-1 antitrypsin deficiency).

Disclosed are products and methods for therapy using nucleic acid molecules, and in particular in relation to treatment of alpha-1-antitrypsin deficiency. Also disclosed are pharmaceutical compositions including the nucleic acids and/or delivery vehicles including the nucleic acids, and their use in manufacture of pharmaceutical compositions for use in therapy, such as treatment of alpha-1-antitrypsin deficiency.

The present invention relates a method for the diagnosis, prediction or risk stratification for mortality and/or disease outcome of a subject that has or is suspected to have sepsis, comprising determining the presence and/or level of antitrypsin (ATT) or fragments thereof in a sample taken from said subject and/or determining the presence and/or level of transthyretin (TTR) or fragments thereof, wherein the presence and/or level of ATT and/or TTR or fragments thereof is correlated with an increased risk of mortality and, wherein said increased risk of mortality and/or poor disease outcome is given if the level of ATT is below a certain cut-off value and/or the level of fragments thereof is above a certain cut-off value and/or said increased risk of mortality and/or poor disease outcome is given if the level of TTR is below a certain cut-off value and/or the level of fragments thereof is below a certain cut-off value. The invention relates in general to the use of ATT and/or TTR or its fragments for the diagnosis of sepsis, and to nucleotides of SEQ ID NO. 2 to 14.