Showing papers in "Molecular Therapy in 2006"

TL;DR: This review is focused on recent developments in the isolation of novel AAV serotypes and isolates, their production and purification, diverse tissue tropisms, mechanisms of cellular entry/trafficking, and capsid structure.

TL;DR: Approval is placed on work with synthetic, small interfering RNAs (siRNAs) published since the first installment of this review which appeared in 2006, and on select publications that demonstrate interesting applications of these principles.

TL;DR: It is shown that immune stimulation by synthetic siRNA can be completely abrogated by selective incorporation of 2'-O-methyl (2'OMe) uridine or guanosine nucleosides into one strand of the siRNA duplex, enabling therapeutically viable siRNA doses without cytokine induction, toxicity, or off-target effects associated with the use of unmodified siRNA.

TL;DR: RAAV9, as well as rAAV8, is a robust vector for gene therapy applications and rAAVs9 is superior to rAAv8 specifically for cardiac gene delivery by systemic vector administration.

TL;DR: Effective in vivo RNA interference was achieved in bronchiole epithelial cells of transgenic EGFP mice after nasal administration of chitosan/siRNA formulations (37% and 43% reduction compared to mismatch and untreated control, respectively).

TL;DR: MSC-Akt improved early repair despite transient engraftment, low levels of cellular fusion, and differentiation, and further confirm the recently reported data that early paracrine mechanisms mediated by MSC are responsible for enhancing the survival of existing myocytes and that Akt could alter the secretion of various cytokines and growth factors.

TL;DR: This work presents the first in vivo evidence indicating that strategies to influence the redox environment of the wound site may have a bearing on healing outcomes.

TL;DR: The AAV 9 vector was found to undergo vector genome transport to distal neuronal cell bodies via known axonal pathways, resulting in correction of lysosomal storage lesions in regions of a diseased brain that would not be corrected if the genome were not transported.

TL;DR: The findings of good tolerability and encouraging responses warrant the continued evaluation of NDV-HUJ in GBM, as well as other cancers.

TL;DR: The study revealed that the concentration window between specific inhibitory function and nonspecific toxicity of the uptake inhibitors was very narrow, and the internalization pathway mediating successful transfection depended on both cell type and polyplex type applied.

TL;DR: The experience of the past 3 years, since the first case of leukemia was reported in a child cured of X-SCID by gene therapy, indicates that the potential genotoxicity of retroviral integration in hematopoietic cells will remain a consideration in evaluating the relative risks versus benefits of gene therapy for specific blood disorders.

TL;DR: Intravenous JX-594 was well tolerated and had highly significant efficacy, including complete responses, against intrahepatic primary tumors in both models, and holds promise as an i.v.-delivered, targeted virotherapeutic.

TL;DR: RNAi has great potential as an antiviral gene therapy approach and support the efforts to develop this strategy for treatment of HIV-1-infected individuals, as well as identify multiple shRNAs that act as potent inhibitors of virus replication.

TL;DR: Findings show that fluid circulation within the CNS through the perivascular space is the primary mechanism by which viral particles and other therapeutic agents administered by CED are spread within the brain and that cardiac contractions power this process.

TL;DR: It is indicated that mRNA electroporation provides a powerful tool to introduce genes into both human and murine primary T lymphocytes by achieving high gene transfection efficiency with low transfections-related toxicity by using in vitro-transcribed mRNA.

TL;DR: This study tested the hypothesis that a hydrophobically modified protein transduction domain, cholesteryl oligo-d-arginine (Chol-R9), may stabilize and enhance tumor regression efficacy of the VEGF-targeting siRNA, and proposed a novel and simple system for the local in vivo application of siRNA through Chol- R9 for cancer therapy.

TL;DR: Introduction of this therapy into the clinic holds promise for Parkinson patients experiencing the motor complications that result from escalating l-Dopa requirements against a background of disease progression.

TL;DR: No partial or complete prostate-specific antigen (PSA) responses were observed; however, 5 patients had a decrease in serum PSA of 25% to 49% following a single treatment, including 3 of 8 patients at the highest dose levels.

TL;DR: It is reported that the in vivo efficacy and safety of PEGylated liposomes systems can be severely compromised following repeat administration, and immunogenicity may be substantially reduced by modifying the alkyl chain of the PEG-lipid conjugate, thereby allowing successful repeat dosing of the modified plasmid formulations without adverse side effects.

TL;DR: It is document successful reconstitution of immune function in a child with the adenosine deaminase (ADA)-deficient form of severe combined immunodeficiency (SCID) following hematopoietic stem cell (HSC) gene therapy.

TL;DR: The combination of both gene-silencing and immunostimulation in one RNA molecule may lead to novel drugs that use both functional activities of RNA as two edges of one sword for effective treatment of viral infection and cancer.

TL;DR: A systematic and quantitative comparison of the cellular uptake and subsequent intracellular distribution of exogenous DNA transfected by viral and nonviral vectors in living cells is described, using a combination of TaqMan PCR and a recently developed confocal image-assisted three-dimensionally integrated quantification method.

TL;DR: Dose-response results in RPE65-mutant dogs indicated that the highest 1.5-log unit range of vector doses proved efficacious, and the efficacy and toxicity limits defined in this study lead to suggestions for the design of a subretinal AAV-2/2.RPE65 human trial of R PE65-associated LCA.

TL;DR: Results demonstrate, for the first time, multiyear FIX expression by AAV2 vector in humans and suggest that improved muscle delivery provides effective treatment for protein deficiencies or muscle-specific diseases.

TL;DR: Both systemic and local administration of exosomes derived from FasL-expressing DC are able to suppress antigen-specific immune responses through an MHC class II-dependent pathway, resulting in effective and sustained treatment of established collagen-induced arthritis and suppression of the DTH inflammatory response.

TL;DR: Analysis of the sequences of the DNA from the junctions of the vector LTR and cellular chromosomes revealed rare integrated NIL vector sequences, which were not mediated by an integrase-driven mechanism due to reversion of the engineered mutations, but more likely were produced by background recombination events.

TL;DR: The efficient AAV8 is promising for animal models of neurodegenerative diseases and potentially as well for gene therapy of brain diseases, although the toxicity observed with GFP expression warrants great caution.

TL;DR: This work built on the prior zinc finger design work of others and in targeting these four genes had a 100% success rate at designing nucleases to the consensus half-site 5'-GNNGNN GNN-3', suggesting that zinc finger nucleases can be empirically designed to stimulate gene targeting in a large portion of the mammalian genome.

TL;DR: It is shown that gene therapy can restore normal vision-dependent behavior in a congenitally blind animal and all parameters of restored retinal health remained stable for at least 7 months.