A5008313599- Virus-based gene therapy research
- Nerve injury and regeneration
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Diverse Musicological Studies
- Prenatal Screening and Diagnostics
- Hemoglobinopathies and Related Disorders
- CAR-T cell therapy research
- Lysosomal Storage Disorders Research
- Viral Infectious Diseases and Gene Expression in Insects
- Neurogenesis and neuroplasticity mechanisms
- Cellular transport and secretion
- Cancer, Hypoxia, and Metabolism
- French Literature and Critical Theory
- RNA regulation and disease
- Mesenchymal stem cell research
- Genetics, Aging, and Longevity in Model Organisms
- Education and Cultural Studies
- Adenosine and Purinergic Signaling
- Spinal Cord Injury Research
- Musicology and Musical Analysis
- Parvovirus B19 Infection Studies
- Single-cell and spatial transcriptomics
- European and International Contract Law
- CRISPR and Genetic Engineering
Harvard University
2024
Boston Children's Hospital
2024
University of Minnesota Medical Center
2024
Massachusetts General Hospital
2024
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2024
Bluebird Bio (United States)
2016-2022
Significance The selective loss of dopaminergic neurons is characteristic Parkinson disease (PD). Protein folding stress a salient feature PD. This study uncovers previously undefined function major unfolded protein response (UPR) transcription factor (XBP1) in supporting the survival nigral at basal levels and under pathological conditions. Our results reveal an important role for canonical UPR pathway maintenance neuron proteostasis, which also could be relevant to understand neuronal...
Gene therapy with LentiGlobin for sickle cell disease (bb1111, lovotibeglogene autotemcel) consists of autologous transplantation a patient's hematopoietic stem cells transduced the BB305 lentiviral vector that encodes βA-T87Q-globin gene. Acute myeloid leukemia developed in woman approximately 5.5 years after she had received as part initial cohort (Group A) HGB-206 study. An analysis peripheral-blood samples revealed blast contained insertion site. The results an investigation causality...
Gene therapy with elivaldogene autotemcel (eli-cel) consisting of autologous CD34+ cells transduced lentiviral vector containing
Spinal cord injury (SCI) is a major cause of paralysis, and involves multiple cellular tissular responses including demyelination, inflammation, cell death axonal degeneration. Recent evidence suggests that perturbation on the homeostasis endoplasmic reticulum (ER) observed in different SCI models; however, functional contribution this pathway to pathology not known. Here we demonstrate triggers fast ER stress reaction (1–3 h) involving upregulation key components unfolded protein response...
Accurate methods to measure autophagic activity in vivo neurons are not available, and most of the studies based on correlative static measurements autophagy markers, leading conflicting interpretations. Autophagy is an essential homeostatic process involved degradation diverse cellular components including organelles protein aggregates. impairment emerging as a relevant factor driving neurodegeneration many diseases. Moreover, strategies modulate have been shown provide protection against...
Abstract Although protein-folding stress at the endoplasmic reticulum (ER) is emerging as a driver of neuronal dysfunction in models spinal cord injury and neurodegeneration, contribution this pathway to peripheral nerve damage remains poorly explored. Here we targeted unfolded protein response (UPR), an adaptive reaction against ER stress, mouse sciatic found that ablation transcription factor XBP1, but not ATF4, significantly delay locomotor recovery. XBP1 deficiency led decreased...
Anelloviridae is a family of non-enveloped viruses with negative-sense, circular, single-stranded deoxyribonucleic acid (ssDNA) genomes that infect vertebrates and are ubiquitous component the human virome. Human anelloviruses evade induction humoral immune responses appear to be non-pathogenic. These properties, in conjunction their enormous genomic diversity wide tissue distribution, make compelling candidates as vectors for next-generation genetic medicines. Here we report first gene...
Niemann-Pick disease is caused by a genetic deficiency in acid sphingomyelinase (ASM) leading to the intracellular accumulation of sphingomyelin and cholesterol lysosomes. In present study, we evaluated effects direct intracerebral transplantation neural progenitor cells (NPCs) on brain storage pathology ASM knock-out (ASMKO) mouse model Type A disease. NPCs derived from adult were genetically modified express human (hASM) transplanted into multiple regions ASMKO brain. Transplanted...
Anelloviridae is a family of single-stranded DNA viruses that are thought to be nonpathogenic and commensal. Despite their ubiquitous presence in human populations, little known about the anellovirus mechanism replication host cells. We identified protein coded by ORF2/3 as necessary sufficient initiate from minimal origin for both Beta- Alphatorquevirus genera. Supporting this observation, we components polymerase alpha BTR complexes interacting with viral initiation (Rip) during...
Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is an X- linked recessive lysosomal disease caused by deficiency of iduronate-2-sulfatase (IDS). Absence IDS results in the accumulation glycosaminoglycans (GAGs) heparan sulfate and dermatan sulfate. Currently only approved treatment option for MPS enzyme replacement therapy (ERT), Elaprase. However, ERT demanding patient does not ameliorate neurological manifestations disease. Using deficient mouse model that phenocopies human...
Betibeglogene autotemcel (beti-cel) gene therapy (GT) for patients with transfusion-dependent β-thalassemia uses autologous CD34+ cells transduced BB305 lentiviral vector (LVV), which encodes a modified β-globin gene. LVV also contains select HIV sequences viral packaging, reverse transcription, and integration. This case report describes patient successfully treated beti-cel in phase 1/2 study (HGB-204; #NCT01745120) subsequently diagnosed wild-type (WT) infection. From 3.5 to 21 months...
Abstract Numerous immune-suppressive mechanisms exist within the tumor microenvironment that may hinder chimeric antigen receptor (CAR) T cell efficacy. One such mechanism is mediated by TGF-β, a cytokine secreted cells and infiltrating suppressive immune directly inhibits effector activity. Effector express TGF-β receptors TGFBR1 TGFBR2, exposure of to induces phosphorylation major signal mediators SMAD2 SMAD3. Phosphorylated SMAD proteins (pSMADs) induce transcriptional program ultimately...
Current manufacturing of clinical grade lentiviral vectors (LVVs) for gene therapy applications commonly relies on transient transfection adherent 293T cells. Improvements in production efficiency and scalability would provide value meeting the needs increased amounts vector required development. An inducible producer cell line grown suspension culture represents a potentially more scalable process LVV which eliminates need costly plasmid reagents. We have engineered packaging by introducing...