This disclosure relates to oligonucleotides, compositions and methods useful for reducing GYS2 expression, particularly in hepatocytes. Disclosed oligonucleotides for the reduction of GYS2 expression may be double-stranded or single-stranded, and may be modified for improved characteristics such as stronger resistance to nucleases and lower immunogenicity. Disclosed oligonucleotides for the reduction of GYS2 expression may also include targeting ligands to target a particular cell or organ, such as the hepatocytes of the liver, and may be used to treat glycogen storage diseases (e.g., GSDIa, GSDIII, GSDIV, GSDVI, and GSDIX) and related conditions.

The present disclosure relates to antisense oligonucleotides (AONs) for modulating the expression of glycogen synthase. AONs of the present disclosure may be useful in treating diseases associated with the modulation of the expression of the enzyme glycogen synthase, such as Pompe disease. Also provided by the present disclosure are compositions comprising AONs, as well as methods of down regulating mRNA coding for glycogen synthase, methods for reducing glycogen synthase in skeletal and cardiac muscle, and methods for treating Pompe disease.

The present disclosure relates to compositions, such as siRNA molecules and FN3 domains conjugated to the same, in combination with enzyme replacement therapies, as well as methods of making and using the same.

The present disclosure relates to antisense oligonucleotides (AONs) for modulating the expression of glycogen synthase. AONs of the present disclosure may be useful in treating diseases associated with the modulation of the expression of the enzyme glycogen synthase, such as Pompe disease. Also provided by the present disclosure are compositions comprising AONs, as well as methods of down regulating mRNA coding for glycogen synthase, methods for reducing glycogen synthase in skeletal and cardiac muscle, and methods for treating Pompe disease.

The present invention discloses mutations in the genes encoding starch synthases and also in starch branching enzymes associated with enhanced dietary fibre and resistant starch levels in the endosperm of a suitable variety of rice. The dietary fiber and resistant starch are enhanced to an extent to significantly reduce the hydrolysis index values of the rice grains to 35%-40%. These rice varieties are in great demand for diabetic population and provide a number of other health benefits such as reduced body weight gain, cardiac health and colon health. As this strategy does not involve the use of genetic manipulation technologies, it can be directly employed in the rice breeding programmers without any restrictions.

Aspects of the disclosure relate to oligonucleotides (e.g., RNAi oligonucleotides such as siRNAs) designed to target GYSI RNAs and targeting complexes for delivering the oligonucleotides to cells (e.g., muscle cells) and uses thereof, particularly uses relating to treatment of disease (e.g., Pompe Disease).

The present disclosure provides methods and compositions for the treatment of glycogen storage disorders, such as, for example, Lafora Disease and adult polyglucosan body disease. The methods and compositions of the present disclosure comprise isolated nucleic acid molecules, rAAV vectors and rAAV viral vectors comprising polynucleotide sequences encoding for artificial micro RNAs (amiRNAs) directed against GYS1.

The present disclosure relates to antisense oligonucleotides (AONs) for modulating the expression of glycogen synthase. AONs of the present disclosure may be useful in treating diseases associated with the modulation of the expression of the enzyme glycogen synthase, such as Pompe disease. Also provided by the present disclosure are compositions comprising AONs, as well as methods of down regulating mRNA coding for glycogen synthase, methods for reducing glycogen synthase in skeletal and cardiac muscle, and methods for treating Pompe disease.

The present disclosure provides methanotrophic bacteria that are modified to produce less glycogen, and methods of using the modified methanotrophic bacteria to produce a desired product, such as protein(s) or metabolite(s).

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of GYSI RNA in a cell or subject, and in certain instances reducing the amount of GYSI protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a glycogen storage disease. Such glycogen storage diseases include Lafora disease, adult polyglucosan body disease (APBD), Andersen's disease, and Pompe disease.