Search results for "CRISPR"
showing 8 items of 68 documents
The Application of CRISPR/Cas9 Technology for Cancer Immunotherapy: Current Status and Problems
2022
Cancer is one of the main causes of disease-related deaths in the world. Although cancer treatment strategies have been improved in recent years, the survival time of cancer patients is still far from satisfied. Cancer immunotherapy, such as Oncolytic virotherapy, Immune checkpoints inhibition, Chimeric antigen receptor T (CAR-T) cell therapy, Chimeric antigen receptor natural killer (CAR-NK) cell therapy and macrophages genomic modification, has emerged as an effective therapeutic strategy for different kinds of cancer. However, many patients do not respond to the cancer immunotherapy which warrants further investigation to optimize this strategy. The clustered regularly interspaced short …
Analysis of the Cellular Roles of MOCS3 Identifies a MOCS3-Independent Localization of NFS1 at the Tips of the Centrosome
2019
The deficiency of the molybdenum cofactor (Moco) is an autosomal recessive disease, which leads to the loss of activity of all molybdoenzymes in humans with sulfite oxidase being the essential protein. Moco deficiency generally results in death in early childhood. Moco is a sulfur-containing cofactor synthesized in the cytosol with the sulfur being provided by a sulfur relay system composed of the L-cysteine desulfurase NFS1, MOCS3, and MOCS2A. Human MOCS3 is a dual-function protein that was shown to play an important role in Moco biosynthesis and in the mcm(5)s(2) U thio modifications of nucleosides in cytosolic tRNAs for Lys, Gln, and Glu. In this study, we constructed a homozygous MOCS3 …
Algunas consideraciones bioéticas y jurídicas acerca de la Declaración de Ginebra sobre edición del genoma humano hereditario a la vista de las Decla…
2021
[ES] La reciente Declaración de Ginebra sobre edición del genoma humano denuncia la posición central que han ocupado tanto la Ciencia como la Bioética hasta la fecha, afirmando que ambas mantienen una posición decididamente favorable respecto a esta bioingeniería, y todo lo cual pone de manifiesto la acuciante necesidad de reorientar el debate hacia el campo del Derecho. El presente artículo tiene por objeto analizar pormenorizadamente las consideraciones vertidas en este documento, formulando interrogantes sobre algunas de ellas, y poniendo en valor la conveniencia de articular un consenso multidisciplinar encabezado por los derechos humanos, en particular, de aquellos grupos más vulnerabl…
A One-Step PCR-Based Assay to Evaluate the Efficiency and Precision of Genomic DNA-Editing Tools
2017
Despite rapid progress, many problems and limitations persist and limit the applicability of gene-editing techniques. Making use of meganucleases, TALENs, or CRISPR/Cas9-based tools requires an initial step of pre-screening to determine the efficiency and specificity of the designed tools. This step remains time consuming and material consuming. Here we propose a simple, cheap, reliable, time-saving, and highly sensitive method to evaluate a given gene-editing tool based on its capacity to induce chromosomal translocations when combined with a reference engineered nuclease. In the proposed technique, designated engineered nuclease-induced translocations (ENIT), a plasmid coding for the DNA-…
Aquaculture as a source of empirical evidence for coevolution between CRISPR-Cas and phage
2019
So far, studies on the bacterial immune system CRISPR-Cas and its ecological and evolutionary effects have been largely limited to laboratory conditions. While providing crucial information on the constituents of CRISPR-Cas, such studies may overlook fundamental components that affect bacterial immunity in natural habitats. Translating laboratory-derived predictions to nature is not a trivial task, owing partly to the instability of natural communities and difficulties in repeated sampling. To this end, we review how aquaculture, the farming of fishes and other aquatic species, may provide suitable semi-natural laboratories for examining the role of CRISPR-Cas in phage/bacterium coevolution…
RAB18 Loss Interferes With Lipid Droplet Catabolism and Provokes Autophagy Network Adaptations
2020
Autophagy is dependent on appropriate lipid supply for autophagosome formation. The regulation of lipid acquisition and the autophagy network response to lipid-limiting conditions are mostly elusive. Here, we show that the knockout of the RAB GTPase RAB18 interferes with lipid droplet catabolism, causing an impaired fatty acid release. The resulting reduced lipid-droplet-derived lipid availability influences autophagy and provokes adaptive modifications of the autophagy network. These adjustments include increased expression and phosphorylation of ATG2B as well as augmented formation of the ATG12-ATG5 conjugate. Moreover, ATG9A shows an enhanced phosphorylation at amino acid residues tyrosi…
Desarrollo de modelos experimentales de LGMDD2 y rastreo de fármacos
2023
La distrofia muscular de cinturas tipo D2 (Limb-girdle muscular dystrophy type D2, LGMDD2) es una enfermedad genética ultra rara para la cual no existe tratamiento. Las principales características clínicas de la LGMDD2 son la debilidad y degeneración muscular progresiva que afecta a las cinturas pélvica y escapular de forma predominante. En 2013 se identificó la LGMDD2 como una miopatía autosómica dominante causada por una mutación en el gen de la transportina 3 (TNPO3), dando como resultado una proteína mutante con una extensión de 15 aminoácidos adicionales: TNPO3mut. TNPO3 es una β-importina responsable de la importación nuclear de proteínas ricas en serina/arginina (proteínas SR), invol…
Edición génica del gen SERPINA1 mediante el uso de CRISPR/Cas9 en células sanguíneas de pacientes con déficit de alfa-1 antitripsina
2022
Introducción. El déficit de alfa-1 antitripsina (DAAT) es una enfermedad rara caracterizada por niveles bajos en sangre de una proteína denominada alfa-1 antitripsina (AAT), principal enzima antiproteasa del suero. El DAAT está provocado por mutaciones en el gen SERPINA1, que codifica para la AAT. Las dos mutaciones más frecuentes se denominan Pi*Z y Pi*S, provocando la primera una sintomatología más grave. A la variante normal se le denomina Pi*M. CRISPR/Cas9 es una herramienta de edición génica adaptada del sistema de inmunidad adquirida presente en bacterias y arqueas que consiste en una endonucleasa, Cas9, guiada por una molécula de RNA simple (sgRNA), complementaria al gen diana. Objet…