RESUMEN
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that leads to the degeneration of motor neurons and the weakening of muscles. Despite extensive research efforts, there is currently no cure for ALS and existing treatments only address its symptoms. To address this unmet medical need, genome editing technologies, such as CRISPR-Cas9, have emerged as a promising solution for the development of new treatments for ALS. Studies have shown that CRISPR-Cas9-guided RNAs have the potential to provide accurate and effective silencing in the genetic disease of ALS. Results have demonstrated a 67% on-target score and a 98% off-target score with GC content within the range of 40-60%. This is further validated by the correlation between the gRNA's structural accuracy and the minimum free energy. The use of CRISPR-Cas9 provides a unique opportunity to target this disease at the molecular level, offering hope for the development of a more effective treatment. In silico and computational therapeutic approaches for ALS suggest that the CRISPR-Cas9 protein holds promise as a future treatment candidate. The CRISPR mechanism and the specificity of gRNA provide a novel therapeutic approach for this genetic disease, offering new hope to those affected by ALS. This study highlights the potential of CRISPR-Cas9 as a promising solution for the development of new treatments for ALS. Further research is required to validate these findings in preclinical and clinical trials and to establish the safety and efficacy of this approach in the treatment of ALS.
Asunto(s)
Esclerosis Amiotrófica Lateral , Humanos , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/terapia , Sistemas CRISPR-Cas/genética , Edición Génica , Músculos , ARN Guía de Sistemas CRISPR-CasRESUMEN
Lactiplantibacillus is among the most extensively studied bacterial specie belonging to the genus Lactobacillus with proven probiotic and health promoting effects. These beneficial effects are generally strains specific but the underlying molecular mechanisms are still not fully understood. Dissecting the determinants behind probiotic topographies of this bacterium is of particular interest since it would help select strains that stand the best chance of success in clinical trials and potential industrial applications. In the current study, we have compared the oleate hydratase phylogeny of seven selected strains of L. plantarum on the basis of their sequence, physiochemical properties and 3D structures. All the strains were assessed on molecular level visualization to find out the active site residues which take part in binding with linoleic acid (LA) at the time of interactions. From the whole genome sequences, the genes responsible for conjugated linoleic acid (CLA) production were identified by Venn diagrams. Identified genes were further compared phylogenetically by MEGA X and physiochemical parameters were analyzed by utilizing ExPaSy-Protparam. The genes were further analyzed for the secondary structures using PSIPRED and tertiary structure was generated by trRosseta and SWISS-MODEL. For the analysis of molecular interactions, LA was used as a ligand and the docking was performed using AutoDock Vina. The phylogenetic analysis showed a close phylogeny of the strains with publicly available genomes. The best interaction energy with LA was observed as -6.7 kcal/mol. The bacteria perform an important role in the CLA production through LA metabolism. Oleate hydratase genes are involved in the complex mechanism of the saturated conversion of LA in to CLA. The current study provides further insights for CLA production by different strains of L. plantarum. There is an excellent opportunity for future studies to investigate different CLA production mechanisms in different bacterial strains.