Showing papers in "Molecular Therapy in 2017"

TL;DR: LNP technology, by virtue of robust and efficient formulation processes, as well as advantages in potency, payload, and design flexibility, will be a dominant non-viral technology to enable the enormous potential of gene therapy.

TL;DR: Of all the molecules evaluated as of January 2017, the regulatory authorities assessed that six provided clear clinical benefit in rigorously controlled trials and the story of these six is given in this review.

TL;DR: This regimen of KTE-C19 was safe for further study in phase 2 and induced durable remissions in patients with refractory DLBCL and demonstrated peak expansion within 2 weeks and continued to be detectable at 12+ months in patientswith ongoing CR.

TL;DR: These data show that LNP-formulated, modified mRNA vaccines can induce protective immunogenicity with acceptable tolerability profiles, demonstrating robust prophylactic immunity in humans.

TL;DR: CARTs are safe, and Cy/Flu can further increase their expansion, which may have contributed to the modest early antitumor responses; the effect of these cells merits further study.

TL;DR: This review focuses on recent advances in NK cell engineering, particularly on preclinical evidence suggesting that NK cells may be as effective as T cells in recognizing and killing targets after genetic modification.

TL;DR: It is demonstrated that CEA CAR-T cell therapy was well tolerated in CEA+ CRC patients even in high doses, and some efficacy was observed in most of the treated patients.

TL;DR: In this paper, the authors compared synthetic mRNA and sa-RNA expressing influenza virus hemagglutinin, and concluded that saRNA is a promising platform for vaccines against viral diseases.

TL;DR: It is demonstrated that activated macrophages secrete mir- 155-enriched exosomes and identify macrophage-derived mir-155 as a paracrine regulator for fibroblast proliferation and inflammation and has the potential to be a therapeutic agent for reducing acute myocardial-infarction-related adverse events.

TL;DR: It is demonstrated that CAR functionality is regulated by target antigen and CAR density and that low expression of either contributes to limited anti-tumor efficacy of the ALK CAR and stoichiometric relationships between CAR receptors and target antigens suggest that manipulation of these parameters could allow precise tuning of CAR T cell activity.

TL;DR: The use of the evolutionarily conserved late-domain (L-domain) pathway is reported as a mechanism for loading exogenous proteins into exosomes and it is demonstrated that labeling of a target protein, Cre recombinase, with a WW tag leads to recognition by the L-domain-containing protein Ndfip1, resulting in ubiquitination and loading intoExosomes.

TL;DR: This work has identified SNPs that either cause or destroy PAM motifs critical for CRISPR-selective editing of one allele versus the other in cells from HD patients and in a transgenic HD model harboring the human allele.

TL;DR: Non-malignant CD19+ B cell recovery with continuing CRs demonstrated that remissions of DLBCL can continue after the disappearance of functionally effective anti-CD19 CAR T cell populations.

TL;DR: The M1 exosomes derived from M1-polarized macrophages proved to be a more potent immunopotentiator than CpG oligonucleotide when used with LCP nanoparticle vaccine in a melanoma growth inhibition study.

TL;DR: In vivo excision of HIV-1 proviral DNA by sgRNAs/saCas9 in solid tissues/organs can be achieved via AAV delivery, a significant step toward human clinical trials.

TL;DR: In anti-CD19 CARs with CD28 costimulatory moieties, lower levels of inflammatory cytokine production and AICD are potential clinical advantages of CD8α hinge and transmembrane domains over CD28 hinge and TS domains.

TL;DR: These findings support the benefit of combining the 4/7 ICR with CAR-PSCA to treat pancreatic cancer, a PSCA-expressing tumor characterized by a dense immunosuppressive environment rich in IL-4.

TL;DR: Human umbilical cord MSC-derived exosome (hucMSC-Ex) administrated by tail vein or oral gavage at different doses and, in engrafted liver mouse models, noted antioxidant and anti-apoptotic effects and rescue from liver failure.

TL;DR: It is shown that modified non-replicating mRNA encoding influenza H10 hemagglutinin and encapsulated in lipid nanoparticles (LNP) induce protective HA inhibition titers and H10-specific CD4+ T cell responses after intramuscular or intradermal delivery in rhesus macaques.

TL;DR: It is shown that miR-155, which is significantly expressed and secreted in Krüppel-like factor 5 (KLF5)-overexpressing vascular smooth muscle cells (VSMCs), is a potent regulator of endothelium barrier function through regulating endothelial targeting tight junction protein expression.

TL;DR: In this article, a CRISPR/Cas9-based approach was proposed for the treatment of patients with Leber congenital amaurosis (LCA) with CEP290 splice mutation.

TL;DR: It is demonstrated that anti-CD19 CAR T cells produced in this manner do not express the endogenous TCR, exhibit potent effector functions in vitro, and mediate clearance of CD19+ tumors in an in vivo mouse model.

TL;DR: Evidence is presented supporting the hypothesis that edible nanoparticles regulate intestinal immune homeostasis by targeting dendritic cells (DCs) by activating AMPK, and orally given nanoparticles isolated from broccoli extracts protect mice against colitis.

TL;DR: A systematic approach is presented for the generation of optimal CARs for effective and selective targeting of tumor-selective targeting of TAAs using the multiple myeloma-associated CD38 antigen as a model system.

TL;DR: It is shown that expression of the circular RNA circ-Amotl1 accelerated healing process in a mouse excisional wound model and discovered that Stat3, similar to Dnmt3a and fibronectin, was a target of miR-17-5p, which led to increased cell adhesion, migration, proliferation, survival, and wound repair.

TL;DR: It is demonstrated, in a humanized mouse model, that the inducible caspase-9 (iC9) safety switch can eliminateCD19.CAR-Ts in a dose-dependent manner, allowing either a selective containment of CD19.

TL;DR: Results of ParvOryx01, the first phase I/IIa clinical trial of an oncolytic parvovirus in recurrent glioblastoma patients, provide an impetus for further H-1PV clinical development.

TL;DR: A CRISPR/Cas9 mediated CCR5 ablating system in long-term HSCs is established, which confers HIV-1 resistance in vivo, and evidence for translating C CR5 gene-edited HSC transplantation for an HIV cure to the clinic is provided.

TL;DR: Exo-AAV is a powerful gene delivery system for hair cell research and may be useful for gene therapy for deafness and shows no toxicity in vivo, as assayed by tests of auditory and vestibular function.

TL;DR: It is suggested that therapeutic antibody administration effectively suppresses EV-triggered metastasis in cancer and that the removal of EVs could be a novel strategy for cancer therapy.