Michael K. Parente

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The lysosomal storage disorders are a large group of inherited diseases that involve central nervous system degeneration. The disease in the brain has generally been refractory to treatment, which will require long-term correction of lesions dispersed throughout the central nervous system to be effective. A promising approach is somatic gene therapy but the(More)
The mucopolysaccharidoses are caused by inherited deficiencies of lysosomal enzymes involved in the degradative pathway of glycosaminoglycans. Lysosomal storage leads to cellular and organ dysfunction, including mental retardation. Storage lesions are found throughout the diseased brain, but little is known about the cellular and molecular mechanisms that(More)
A wide diversity of adeno-associated virus (AAV) structural proteins uncovered from latent genomes in primate tissue has expanded the number of AAV vector serotypes, which can potentially confer unique cell tropism to the vector. We evaluated 17 of these vectors in the mouse brain using green fluorescent protein (GFP) as a reporter gene. A rapid initial(More)
A number of different transfection reagents have been used for lentiviral vector production. We directly compared transfection buffers, DNA purification methods, chemical facilitators, and DNA concentrations to optimize production. The use of N,N-bis (2-hydroxyethyl)-2-aminoethanesulfonic acid (BES), sodium butyrate, and one fourth the total amount of DNA(More)
The characteristic neurological feature of many neurogenetic diseases is intellectual disability. Although specific neuropathological features have been described, the mechanisms by which specific gene defects lead to cognitive impairment remain obscure. To gain insight into abnormal functions occurring secondary to a single gene defect, whole transcriptome(More)
Down-regulation of retroviral vector expression occurs in a number of cell types after transplantation. Although a number of vector elements have been shown to affect expression in specific experimental situations, the results can vary depending on the specific cDNA being expressed, the individual retroviral elements included in vectors, the promoter, or(More)
Gene therapy has been at least partially effective in several mouse disease models, but treatment of large mammals has been more difficult to achieve. One major limitation is that only low levels of expression of the corrective gene are often maintained in vivo. In a mouse model of the lysosomal storage disease mucopolysaccharidosis (MPS) type VII (Sly(More)
Retrovirus vectors were constructed to transfer and express the cDNA of the human lysosomal acid hydrolase beta-glucuronidase (GUSB) under control of the human GUSB promoter. Expression of the transcription unit (minigene) was evaluated in a GUSB-negative cell line established from a mouse with the lysosomal storage disease mucopolysaccharidosis (MPS) type(More)
The neurogenetic, lysosomal enzyme (LSE) deficiency diseases are characterized by storage lesions throughout the brain; therefore, gene transfer needs to provide widespread distribution of the normal enzyme. Adeno-associated virus (AAV) vectors can be effective in the brain despite limited transduction because LSEs are exported to neighboring cells(More)
Retrovirus vector titers could be increased by more than 50-fold after multiple superinfections of packaging cells with vector virus expressing a complementing host-range envelope glycoprotein. The high level of expression was stable for at least 90 passages in culture. The optimum conditions for density of cell seeding, length of incubation, and temporary(More)