Abstract: The present invention provides a polypeptide therapeutic agent, useful in enzyme replacement therapy, with increased therapeutic benefits for the central nervous system. The invention provides a method of enhancing the effect of a polypeptide or protein on the central nervous system by the attachment of a short acidic amino acid sequence. Specifically the inventors disclose the attachment of a 4-15 acidic amino acid sequence to human ?-glucuronidase by construction of a fusion protein. This molecule is useful in the treatment of type VII mucopolysaccharidosis when administered to a patient.

Abstract: This invention relates to compositions and methods of delivering therapeutic agents to bone. More specifically, the invention relates to endowing a large molecule vectors i.e., adeno virus, retrovirus, liposomes, micelles, natural and synthetic polymers, or combinations thereof, with the ability to target bone tissue in vivo and with improved stability in the blood, by attaching multiple copies of acid amino acid peptides. One preferred embodiment of the invention relates to endowing an adeno-associated virus (AAV) vector with the ability to target bone-tissue in vivo and improve its stability, by the addition of multiple acidic amino acid peptides attached to the capsid of the viral vector.

Abstract: The present invention provides compositions and methods for use in enzyme replacement therapy. The inventors disclose a method of producing membrane bound enzymes in an active soluble form by eliminating the glycosylphosphatidylinositol (GPI) membrane anchor. In particular the inventors disclose a soluble active form of the membrane bound enzyme TNSALP which they produced by deleting the GPI anchor single peptide sequence. They have further shown that this composition is useful for treatment of hypophosphatasia. The inventors also disclose oligo acid amino acid variants thereof which specifically target bone tissue.

Abstract: This invention relates generally to compositions and methods which utilization nuclear receptors for regulating adipogenesis in cells. Specifically, the invention is directed to compositions which regulate transcription factor PPAR?. and enhance or inhibit the transcription of genes responsible for directing cell differentiation towards a pathway of adipogenesis. More specifically, disclosed herein is a novel polypeptide coactivator of PPAR?, and fragments thereof, which possess coactivator or corepressor activity. Also related are nucleotide sequences which express these polypeptides. Also disclosed is an interfering RNA that may be used to inhibit adipogenesis.

Abstract: A method of producing a polydeoxyribonucleotide molecule by reverse transcriptase polymerase chain reaction wherein the polydeoxyribonucleotide molecule has a length of greater than 5,000 base-pairs is disclosed. The method involves combining two reverse transcriptases followed by two protocols of polymerase chain reaction. This method enable the amplification of large DNAs, such as viruses, from a sample while preserving genetic diversity of the large DNA.