Abstract: Provided are isolated nucleic acids for expressing lysosomal polypeptides such as lysosomal acid ?-glucosidase (GAA) and vectors comprising the same. The invention provides an isolated nucleic acid encoding a chimeric polypeptide comprising a secretory signal sequence operably linked to a lysosomal polypeptide. The invention also provides an isolated nucleic acid comprising a coding region encoding a GAA and a GAA 3? untranslated region (UTR), wherein the GAA 3? UTR comprises a deletion therein. The invention further provides an isolated nucleic acid comprising a coding region encoding a GAA and a 3? UTR wherein the 3? UTR is less than about 200 nucleotides in length and comprises a segment that is heterologous to the GAA coding region. Also provided are methods of making and using delivery vectors encoding lysosomal polypeptides to produce the lysosomal polypeptide to treat subjects afflicted with a deficiency in the lysosomal polypeptide.

Abstract: The present invention relates, in general, to a method of treating patients undergoing enzyme replacement therapy (ERT) or other therapy involving the administration of a proteinaceous therapeutic agent as well gene replacement therapy with non-viral or viral vectors, or other therapeutic modality or modalities, used alone or in combination, which involve the administration of exogenous substances for potential therapeutic benefit, including, but not limited to DNA vaccines, siRNA, splice-site switching oligomers (SSOs) as well as RNA-based nanoparticles (RNPs) and nanovaccines. The invention further relates to compounds and compositions suitable for use in such methods.

Abstract: The present invention relates, in general, to a method of treating patients undergoing enzyme replacement therapy (ERT) or other therapy involving the administration of a proteinaceous therapeutic agent as well gene replacement therapy with non-viral or viral vectors, or other therapeutic modality or modalities, used alone or in combination, which involve the administration of exogenous substances for potential therapeutic benefit, including, but not limited to DNA vaccines, siRNA, splice-site switching oligomers (SSOs) as well as RNA-based nanoparticles (RNPs) and nanovaccines. The invention further relates to compounds and compositions suitable for use in such methods.

Abstract: The present invention relates, in general, to Pompe disease and, in particular, to a methods of treating Pompe disease and to compounds/constructs suitable for use in such methods.

Abstract: The present invention relates, in general, to Pompe disease and, in particular, to a methods of treating Pompe disease and to compounds/constructs suitable for use in such methods.

Abstract: The present invention relates, in general, to a method of treating patients undergoing enzyme replacement therapy (ERT) or other therapy involving the administration of a proteinaceous therapeutic agent as well gene replacement therapy with non-viral or viral vectors, or other therapeutic modality or modalities, used alone or in combination, which involve the administration of exogenous substances for potential therapeutic benefit, including, but not limited to DNA vaccines, siRNA, splice-site switching oligomers (SSOs) as well as RNA-based nanoparticles (RNPs) and nanovaccines. The invention further relates to compounds and compositions suitable for use in such methods.

Abstract: The present invention relates, in general, to a method of treating patients undergoing enzyme replacement therapy (ERT) or other therapy involving the administration of a proteinaceous therapeutic agent as well gene replacement therapy with non-viral or viral vectors, or other therapeutic modality or modalities, used alone or in combination, which involve the administration of exogenous substances for potential therapeutic benefit, including, but not limited to DNA vaccines, siRNA, splice-site switching oligomers (SSOs) as well as RNA-based nanoparticles (RNPs) and nanovaccines. The invention further relates to compounds and compositions suitable for use in such methods.

Abstract: Methods of treating a lysosomal storage disorder and methods of increasing cellular uptake of a lysosomal enzyme using ?2 agonists or therapeutic agents that increase expression of receptors for a lysosomal enzyme.

Abstract: The present invention relates, in general, to a method of treating patients undergoing enzyme replacement therapy (ERT) or other therapy involving the administration of a proteinaceous therapeutic agent as well gene replacement therapy with non-viral or viral vectors, or other therapeutic modality or modalities, used alone or in combination, which involve the administration of exogenous substances for potential therapeutic benefit, including, but not limited to DNA vaccines, siRNA, splice-site switching oligomers (SSOs) as well as RNA-based nanoparticles (RNPs) and nanovaccines. The invention further relates to compounds and compositions suitable for use in such methods.

Abstract: Provided are isolated nucleic acids for expressing lysosomal polypeptides such as lysosomal acid ?-glucosidase (GAA) and vectors comprising the same. The invention provides an isolated nucleic acid encoding a chimeric polypeptide comprising a secretory signal sequence operably linked to a lysosomal polypeptide. The invention also provides an isolated nucleic acid comprising a coding region encoding a GAA and a GAA 3? untranslated region (UTR), wherein the GAA 3? UTR comprises a deletion therein. The invention further provides an isolated nucleic acid comprising a coding region encoding a GAA and a 3? UTR wherein the 3? UTR is less than about 200 nucleotides in length and comprises a segment that is heterologous to the GAA coding region. Also provided are methods of making and using delivery vectors encoding lysosomal polypeptides to produce the lysosomal polypeptide to treat subjects afflicted with a deficiency in the lysosomal polypeptide.

Abstract: Methods of treating a lysosomal storage disorder and methods of increasing cellular uptake of a lysosomal enzyme using ?2 agonists or therapeutic agents that increase expression of receptors for a lysosomal enzyme.

Abstract: A recombinant hybrid virus, including: (a) a deleted adenovirus vector genome comprising the adenovirus 5? and 3? cis-elements for viral replication and encapsidation, and further comprising a deletion in an adenovirus genomic region selected from the group consisting of: (i) the polymerase region, wherein said deletion essentially prevents the expression of a functional polymerase protein from said deleted region and said hybrid virus does not otherwise express a functional polymerase protein, (ii) the preterminal protein region, wherein said deletion essentially prevents the expression of a functional preterminal protein from said deleted region, and said hybrid virus does not otherwise express a functional preterminal protein, and (iii) both the regions of (i) and (ii); and (b) a recombinant adeno-associated virus (AAV) vector genome flanked by the adenovirus vector genome sequences of (a), said recombinant AAV vector genome comprising (i) AAV 5? and 3? inverted terminal repeats, (ii) an AAV packaging sequ

Abstract: The present invention relates, in general, to Pompe disease and, in particular, to a methods of treating Pompe disease and to compounds/constructs suitable for use in such methods.

Abstract: A recombinant hybrid virus which includes: (a) a deleted adenovirus vector genome having the adenovirus 5? and 3? cis-elements for viral replication and encapsidation and a deletion in an adenovirus genomic region selected from the polymerase region and/or the preterminal protein region, wherein the deletion essentially prevents the expression of a functional polymerase and/or preterminal protein from the deleted region and the hybrid virus does not otherwise express a functional polymerase protein; and (b) a recombinant adeno-associated virus (AAV) vector genome flanked by the adenovirus vector genome sequences of (a), wherein the recombinant AAV vector genome includes an AAV packaging sequence and a heterologous nucleic acid sequence, wherein the heterologous nucleic acid sequence is flanked by 5? and 3? AAV inverted terminal repeats.

Abstract: The present invention provides replicating [100K?] adenovirus vectors that have an impairment in 100K activity. In particular preferred embodiments, the impairment is the result of a deletion in the 100K coding region of the adenovirus vector genome. It is further preferred that the adenovirus produces the E1 gene products. In an alternate embodiment, the adenovirus produces the E1a gene products, but has an impairment in the E1b coding region, such that replication of the virus is limited to p53? cells. Also described are methods of making and administering the inventive adenovirus vectors to a cell or to a subject. Further provided is use of the inventive [100K?] Ad vectors as a helper virus for the production of vector stocks of adeno-associated virus.

Abstract: Provided are isolated nucleic acids for expressing lysosomal polypeptides such as lysosomal acid &agr;-glucosidase (GAA) and vectors comprising the same. In one embodiment, the invention provides an isolated nucleic acid encoding a chimeric polypeptide comprising a secretory signal sequence operably linked to a lysosomal polypeptide. In another representative embodiment, an isolated nucleic acid is provided comprising a coding region encoding a GAA and a GAA 3′ untranslated region (UTR), wherein the GAA 3′ UTR comprises a deletion therein. In another representative embodiment, the invention provides an isolated nucleic acid comprising a coding region encoding a GAA and a 3′ UTR, wherein the 3′ UTR is less than about 200 nucleotides in length and comprises a segment that is heterologous to the GAA coding region.

Abstract: The present invention provides replicating [100K−] adenovirus vectors that have an impairment in 100K activity. In particular preferred embodiments, the impairment is the result of a deletion in the 100K coding region of the adenovirus vector genome. It is further preferred that the adenovirus produces the E1 gene products. In an alternate embodiment, the adenovirus produces the E1a gene products, but has an impairment in the E1b coding region, such that replication of the virus is limited to p53− cells. Also described are methods of making and administering the inventive adenovirus vectors to a cell or to a subject. Further provided is use of the inventive [100K−] Ad vectors as a helper virus for the production of vector stocks of adeno-associated virus.