Showing papers in "Molecular Therapy in 2015"

TL;DR: Current knowledge related to the potential use of MSC-derived EVs in various diseases is reviewed and the promising future for EVs as an alternative, cell-free therapy is discussed.

TL;DR: It is shown that chemically unmodified mRNA can achieve sufficient protein expression and avoid activation of the innate immune system by applying sequence-engineered molecules, and has the potential to revolutionize human protein therapies.

TL;DR: Observations warrant further research on CART-33 treatment in refractory AML and may spur efforts to extend the Cart-33-induced tumor burden to the preparation of other intensive strategies, such as hematopoietic stem cell transplantation.

TL;DR: It is demonstrated that it is feasible to engineer CAR-expressing NK cells as a clonal, molecularly and functionally well-defined and continuously expandable cell therapeutic agent, and suggested NK-92/5.28.

TL;DR: Local macrophage-derived IGF-1 is established as a key factor in inflammation resolution and macrophages polarization during muscle regeneration in injured muscle.

TL;DR: A detailed analysis of transduction levels throughout the brain, brainstem, and spinal cord of nonhuman primates is presented, providing new guidance for translation toward therapy for a wide range of neurodegenerative disorders.

TL;DR: In this paper, the miR-197/CKS1B/STAT3-mediated PD-L1 network was identified in chemoresistant non-small-cell lung cancer.

TL;DR: Benefit showing reduced endomysial fibrosis, reduced central nucleation, more normal fiber size distribution with muscle hypertrophy, especially at high dose is encouraging for treatment of dystrophin-deficient muscle diseases.

TL;DR: Preclinical data supports the clinical application of CAR T cells additionally modified to constitutively express CD40L with anticipated enhanced antitumor efficacy.

TL;DR: The results support the clinical relevance of a minimally invasive AAV-mediated optogenetic therapy for visual restoration and show that AAV encoding channelrhodopsin under the ON bipolar cell-specific promoter mediates long-term gene delivery restricted to ON-bipolar cells after intravitreal administration.

TL;DR: PCT is an emerging approach based on small-molecule ligands that selectively bind and stabilize mutant enzymes, increase their cellular levels, and improve lysosomal trafficking and activity that shows advantages, particularly in terms of oral administration, broad biodistribution, and positive impact on patients' quality of life.

TL;DR: Oncolysis of the primary tumor significantly abrogated systemic resistance to PD-1-immunotherapy leading to improved elimination of disseminated lung tumors and combined treatment completely inhibited dissemination in a CD8 T-cell-dependent manner.

TL;DR: The results demonstrate the advantages of the CRISPR/Cas9 system in allele-specific genome targeting and in NHEJ-mediated gene disruption.

TL;DR: It is suggested that optimal CAR function may require the elimination of cellular FcγR interactions to improve T cell persistence and antitumor responses.

TL;DR: It is shown that Gas5 suppresses tumor malignancy by downregulating miR-222, which may serve as a promising therapy for glioma.

TL;DR: Given the acceptable safety profile of multiple intravenous Pexa-Vec infusions in patients with treatment-refractory colorectal cancer, further trials evaluating efficacy of intravenously PX-594, as monotherapy or in combination with chemotherapeutic agents, is warranted in this patient population.

TL;DR: Short versions of the mitoTALEN specific for the MERRF m.8344A>G mutation are designed, which will improve the ability to package these large sequences into viral vectors, bringing the use of these genetic tools closer to clinical trials.

TL;DR: Overall, this study suggests Pexa-Vec is safe to administer to pediatric patients by intratumoral administration and could be studied further in this patient population.

TL;DR: This report represents the first identification of a natural target of a tRF and illustrates how a virus utilizes a host tRF to control a host gene to favor its replication.

TL;DR: In vivo tests indicated that let-7 inhibition promoted SCs migration and axon outgrowth within a regenerative microenvironment and the inhibitory effect ofLet-7 miRNAs on SCs apoptosis might serve as an early stress response to nerve injury, but this effect seemed to be not mediated through a NGF-dependent pathway.

TL;DR: In this paper, the authors used RNA-sequencing to identify lncRNAs related to renal inflammation and fibrosis in obstructive nephropathy induced in Smad3 wild-type and knockout mice.

TL;DR: It is determined that CAR-modified HSPCs differentiate into functional T cells as well as natural killer cells in vivo in humanized mice and these cells are resistant to HIV infection and suppress HIV replication, suggesting that stem cell-based gene therapy with a CAR may be feasible and effective in treating chronic HIV infection.

TL;DR: Both the light responses of the retinal explants and the visually-guided behavior occurred reliably at light levels that were two to three orders of magnitude dimmer than required for channelrhodopsin, presenting a novel approach to impart light sensitivity for visual restoration in a useful range of illumination.

TL;DR: In summary, intratumoral injection of the oncolytic vaccinia vvDD was well-tolerated in patients and resulted in selective infection of injected and noninjected tumors and antitumor activity.

TL;DR: This study demonstrates a powerful method to restore the dystrophin reading frame and protein expression by permanently deleting exons through genome editing with zinc finger nucleases.

TL;DR: It is demonstrated that pol III-driven shRNAs lead to significantly increased knockdown but also increased cytotoxcity in comparison to pol II-driven miRNA adapted shRNA(miR)s in multiple hematopoietic cell lines, suggesting the requirement for optimization of shRNA sequences upon incorporation into a miRNA backbone.

TL;DR: It is demonstrated that CYL-02 nonviral gene therapy has a favorable safety profile and is well tolerated in patients and predictive biomarkers of response to treatment were identified, and these promising results warrant further evaluation in phase 2 clinical trial.

TL;DR: Observations suggest that high levels of inflammatory cytokines alone or in combination with semi-acute heart failure and epileptic seizure may have contributed substantially to the occurrence of the acute and lethal event.

TL;DR: It is reported that unilateral subretinal delivery of an adeno-associated virus serotype 5 (AAV5) vector carrying either the mouse or the human intact CNGA3 gene under the control of the red/green opsin promoter results in long-term recovery of visual function inCNGA3-mutant sheep.

TL;DR: It is shown that three-dimensional scaffolds generated from decellularized mouse thymus can support thymic epithelial cell survival in culture and maintain their unique molecular properties.