Described herein are compositions and methods for tissue-targeted expression of therapeutic genes, using AAV expression vectors that reduce the risk of toxicity associated with AAV gene therapy in the CNS by de-targeting the vulnerable neurons cells including the DRG cells on gene expression, and de-targeting the liver, a major suspect for over-expression in the periphery.

Described herein are compositions and methods for tissue-targeted expression of therapeutic genes, using AAV expression vectors that reduce the risk of toxicity associated with AAV gene therapy in the CNS by de-targeting the vulnerable neurons cells including the DRG cells on gene expression, and de-targeting the liver, a major suspect for over-expression in the periphery.

The present invention is directed to a method of inactivating virus that is present during production of a polypeptide of interest. In particular, the present invention is directed to a method of on-column virus inactivation using a low pH and high salt wash solution that effectively inactivates viruses with minimum recovery loss of the polypeptide.

The present invention is directed to a method of inactivating virus that is present during production of a polypeptide of interest. In particular, the present invention is directed to a method of on-column virus inactivation using a low pH and high salt wash solution that effectively inactivates viruses with minimum recovery loss of the polypeptide.

Liver-specific promoters and application thereof are provided. A set of small-size recombinant nucleic acid sequences for regulating high specific expression of genes in a liver system are provided. Compared with the currently reported other sequences of similar size, the said recombinant regulatory sequence fragment has the advantage that the ability of driving expression of reporter gene and human coagulation factor FVIII in the liver system is significantly enhanced, thereby being suitable for recombinant adeno-associated virus (rAAV)-mediated gene therapy.

Liver-specific promoters and application thereof are provided. A set of small-size recombinant nucleic acid sequences for regulating high specific expression of genes in a liver system are provided. Compared with the currently reported other sequences of similar size, the said recombinant regulatory sequence fragment has the advantage that the ability of driving expression of reporter gene and human coagulation factor FVIII in the liver system is significantly enhanced, thereby being suitable for recombinant adeno-associated virus (rAAV)-mediated gene therapy.

The present disclosure relates to agents, compositions targeting to von Willebrand factor (VWF). The VWF targeting agents are synthetic polynucleotides, including VWF binding agents and their reversal agents. The VWF binding agents are VWF binding aptamers that bind to and inhibit the VWF activities. The VWF binding agents can be reversed using reversal agents to reverse the inhibitory effect and thereby restore VWF activities. The disclosure further provides methods for regulating the activities of VWF, thereby modulating VWF mediated platelet functionality, such as thrombosis. the present VWF targeting agents may be used for preventing thrombus formation and treating thrombotic disorders.

The present invention provides multi-armed high MW polymers containing hydrophilic groups conjugated to Factor VIII, and methods of preparing such polymers.

The present invention provides multi-armed high MW polymers containing hydrophilic groups conjugated to Factor VIII, and methods of preparing such polymers.

An optimized coding sequence of human blood clotting factor eight (VIII) and a promoter may be used in vectors, such as rAAV, for introduction of factor VIII, and/or other blood clotting factors and transgenes. Exemplary of these factors and transgenes arc alpha-1-antitrypsin, as well as those involved in the coagulation cascade, hepatocye biology, lysosomal storage, urea cycle disorders, and lipid storage diseases. Cells, vectors, proteins, and glycoproteins produced by cells transformed by the vectors and sequence, may be used in treatment.