AI Article Synopsis
Article Abstract
Genome instability is a hallmark of cancer. Common fragile sites (CFSs) are specific regions in the human genome that are sensitive to replication stress and are prone to genomic instability in different cancer types. Here we molecularly cloned a new CFS, FRA11H, in 11q13. The genomic region of FRA11H harbors a hotspot of chromosomal breakpoints found in different types of cancer, indicating that this region is unstable during cancer development. We further found that FRA11H is a hotspot for integrations of Murine Leukemia Virus (MLV)-based vectors, following CD34+ infections in vitro as well as ex-vivo during gene therapy trials. Importantly, we found that the MLV-based vector infection in-vitro leads to replication perturbation, DNA damage and increased CFS expression. This suggests that infection by MLV-based vectors leads to replication-induced genome instability, raising further concerns regarding the use of retroviral vectors in gene therapy trials.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711054 | PMC |
| http://dx.doi.org/10.1038/srep02189 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Development of Lentiviral Packaging Cells and Scale Up of Production to Meet the Growing Demand in Cell and Gene Therapy.
Curr Gene Ther
January 2025
Research Group Medical Biotechnology & Bioengineering, TH Köln - University of Applied Sciences, Leverkusen, Germany.
Gamma-Retroviral (RVVs) and lentiviral vectors (LVVs) represent indispensable tools in somatic gene therapy, mediating the efficient, stable transfer of therapeutic genes into a variety of human target cells. LVVs, in contrast to RVVs, are capable of stably genetically modifying non-proliferating target cells, making them the superior instrument in cell and gene therapy. To date, the LVV manufacturing process employs human embryonic kidney cells (HEK293) and derivatives thereof transiently transfected with multiple plasmids encoding the required viral vector components.
View Article and Find Full Text PDFDevelopment of a latency model for HIV-1 subtype C and the impact of long terminal repeat element genetic variation on latency reversal.
J Virus Erad
December 2024
HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Sub-Saharan Africa accounts for almost 70 % of people living with HIV (PLWH) worldwide, with the greatest numbers centred in South Africa where 98 % of infections are caused by subtype C (HIV-1C). However, HIV-1 subtype B (HIV-1B), prevalent in Europe and North America, has been the focus of most cure research and testing despite making up only 12 % of HIV-1 infections globally. Development of latency models for non-subtype B viruses is a necessary step to address this disproportionate focus.
View Article and Find Full Text PDFFucosidosis: A Review of a Rare Disease.
Int J Mol Sci
January 2025
Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Çanakkale 17100, Turkey.
Fucosidosis is a rare lysosomal storage disease caused by α-L-fucosidase deficiency following a mutation in the gene. This enzyme is responsible for breaking down fucose-containing glycoproteins, glycolipids, and oligosaccharides within the lysosome. Mutations in result in either reduced enzyme activity or complete loss of function, leading to the accumulation of fucose-rich substrates in lysosomes.
View Article and Find Full Text PDFLentivirus-mediated gene therapy for Fabry disease: 5-year End-of-Study results from the Canadian FACTs trial.
Clin Transl Med
January 2025
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Background: Fabry disease is an X-linked lysosomal storage disorder due to a deficiency of α-galactosidase A (α-gal A) activity. Our goal was to correct the enzyme deficiency in Fabry patients by transferring the cDNA for α-gal A into their CD34+ hematopoietic stem/progenitor cells (HSPCs). Overexpression of α-gal A leads to secretion of the hydrolase; which can be taken up and used by uncorrected bystander cells.
View Article and Find Full Text PDFMechanism-guided engineering of a minimal biological particle for genome editing.
Proc Natl Acad Sci U S A
January 2025
Innovative Genomics Institute, University of California, Berkeley, CA 94720.
The widespread application of genome editing to treat and cure disease requires the delivery of genome editors into the nucleus of target cells. Enveloped delivery vehicles (EDVs) are engineered virally derived particles capable of packaging and delivering CRISPR-Cas9 ribonucleoproteins (RNPs). However, the presence of lentiviral genome encapsulation and replication proteins in EDVs has obscured the underlying delivery mechanism and precluded particle optimization.
View Article and Find Full Text PDFWant 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!