Background: In previous clinical trials involving children with X-linked severe combined immunodeficiency (SCID-X1), a Moloney murine leukemia virus-based γ-retrovirus vector expressing interleukin-2 receptor γ-chain (γc) complementary DNA successfully restored immunity in most patients but resulted in vector-induced leukemia through enhancer-mediated mutagenesis in 25% of patients. We assessed the efficacy and safety of a self-inactivating retrovirus for the treatment of SCID-X1.
Methods: We enrolled nine boys with SCID-X1 in parallel trials in Europe and the United States to evaluate treatment with a self-inactivating (SIN) γ-retrovirus vector containing deletions in viral enhancer sequences expressing γc (SIN-γc).
Results: All patients received bone marrow-derived CD34+ cells transduced with the SIN-γc vector, without preparative conditioning. After 12.1 to 38.7 months of follow-up, eight of the nine children were still alive. One patient died from an overwhelming adenoviral infection before reconstitution with genetically modified T cells. Of the remaining eight patients, seven had recovery of peripheral-blood T cells that were functional and led to resolution of infections. The patients remained healthy thereafter. The kinetics of CD3+ T-cell recovery was not significantly different from that observed in previous trials. Assessment of insertion sites in peripheral blood from patients in the current trial as compared with those in previous trials revealed significantly less clustering of insertion sites within LMO2, MECOM, and other lymphoid proto-oncogenes in our patients.
Conclusions: This modified γ-retrovirus vector was found to retain efficacy in the treatment of SCID-X1. The long-term effect of this therapy on leukemogenesis remains unknown. (Funded by the National Institutes of Health and others; ClinicalTrials.gov numbers, NCT01410019, NCT01175239, and NCT01129544.).
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274995 | PMC |
| http://dx.doi.org/10.1056/NEJMoa1404588 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
RetinaRegNet: A zero-shot approach for retinal image registration.
Comput Biol Med
January 2025
Department of Electrical and Computer Engineering, University of Florida, Gainesville, FL, 32610, United States; Department of Medicine, University of Florida, Gainesville, FL, 32610, United States; Department of Health Outcomes and Biomedical Informatics, University of Florida, Gainesville, FL, 32610, United States; Intelligent Clinical Care Center, University of Florida, Gainesville, FL, 32610, United States. Electronic address:
Retinal image registration is essential for monitoring eye diseases and planning treatments, yet it remains challenging due to large deformations, minimal overlap, and varying image quality. To address these challenges, we propose RetinaRegNet, a multi-stage image registration model with zero-shot generalizability across multiple retinal imaging modalities. RetinaRegNet begins by extracting image features using a pretrained latent diffusion model.
View Article and Find Full Text PDFObservation of broadband super-absorption of electromagnetic waves through space-time symmetry breaking.
Sci Adv
January 2025
School of Electrical and Computer Engineering, Cornell University, Ithaca, NY 14853, USA.
Using time as an additional design parameter in electromagnetism, photonics, and wave physics is attracting considerable research interest, motivated by the possibility to explore physical phenomena and engineering opportunities beyond the limits of time-invariant systems. Here, we report the experimental demonstration of enhanced broadband absorption of electromagnetic waves in a continuously modulated time-varying system, exceeding one of the key theoretical limits of linear time-invariant absorbers. This is achieved by harnessing the frequency-wave vector transitions and enhanced interference effects enabled by breaking both continuous space- and time-translation symmetries in a periodically time-modulated absorbing structure operating at radio frequencies.
View Article and Find Full Text PDFThe value co-creation mechanism of Public Cultural Services ecosystem in China based on "public value" theory.
PLoS One
January 2025
Faculty of Humanities and Social Sciences, Macao Polytechnic University, Macao, Macao.
The establishment of China's public cultural service system has been explored for nearly two decades, but there is still a significant gap in achieving the goal of equalising and eliminating differences in public value, and it is urgent to systematically explore the public value governance issues contained in it. This paper presents a localised theoretical analysis framework based on the strategic triangle model of public value, with the objective of exploring the endogenous mechanism of China's public cultural services ecosystem (PCSE). Furthermore, it constructs a panel vector autoregression (PVAR) model from a dynamic endogenous perspective, employing the STATA 16.
View Article and Find Full Text PDFRaw bioelectrical impedance parameters and vector analysis in the screening of low muscle mass and low muscle mass associated with obesity in adult healthy subjects.
Intern Emerg Med
January 2025
Central Laboratory of Clinical Biology, Frantz Fanon Hospital, University Hospital Center of Blida, 9000, Blida, Algeria.
The aim was to estimate the prevalence of low muscle mass (LMM) and low muscle mass associated with obesity (LMM-O) in healthy adult, and to verify the performance of raw bioelectrical impedance parameters (BIA) and vector analysis (BIVA) in the screening of this tow conditions. This is a cross-sectional study including 1025 healthy adults. Body composition was assessed by the BIA technique.
View Article and Find Full Text PDFRetrospective discrimination of PNES and epileptic seizure types using blood RNA signatures.
J Neurol
January 2025
Morehouse School of Medicine, Neuroscience Institute, 720 Westview Drive SW, Atlanta, GA, 30310, USA.
Objectives: The ability to differentiate epileptic- and non-epileptic events is challenging due to a lack of reliable molecular seizure biomarker that provide a retrospective diagnosis. Here, we use next generation sequencing methods on whole blood samples to identify changes in RNA expression following seizures.
Methods: Blood samples were obtained from 32 patients undergoing video electroencephalogram (vEEG) monitoring.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!