The bluetongue virus (BTV), transmitted by biting midges, poses a significant threat to livestock globally. This orbivirus induces bluetongue disease, leading to substantial economic losses in the agricultural sector. The current control measures have limitations, necessitating the development of novel, efficient vaccines. In this study, an immunoinformatics approach is employed to design a multi-epitope subunit vaccine for Ovis aries targeting six BTV serotypes. Focusing on the VP2 capsid protein, the vaccine incorporates B-cell, helper-T lymphocytes (HTL), and cytotoxic T-cell lymphocytes (CTL) epitopes. Molecular docking reveals stable interactions with TLR2 and TLR4 receptors, suggesting the stability of the complex, indicating the potential viability of the multi-epitope vaccine. The computational approach offers a rapid and tailored strategy for vaccine development, highlighting potential efficacy and safety against BTV outbreaks. This work contributes to understanding BTV and presents a promising avenue for effective control.
Autism Spectrum Disorder (ASD) is a genetically heterogeneous neurodevelopmental condition driven by rare de novo variants, copy number variations, and polygenic risk. SFARI-curated genes show high mutational constraint and enriched expression in cortical neurons and glia. This review highlights recent advances in CRISPR-based functional genomics using human pluripotent stem cells and induced pluripotent stem cells differentiated into neural progenitors, excitatory and inhibitory neurons, astrocytes, microglia, and brain organoids. CRISPR modalities including knockouts, CRISPRi and CRISPRa, base and prime editing, and Cas13 enable pooled and arrayed screens with high coverage at low multiplicity of infection. Integration of multimodal readouts such as Perturb-seq, single-cell and spatial transcriptomics, proximity labeling proteomics, and functional assays including microelectrode arrays and calcium imaging provides system-level insights into ASD gene function. Computational frameworks like MIMOSCA and SCEPTRE facilitate network reconstruction and pseudo-time inference. Case studies reveal Wnt and BAF complex dysregulation, microglial pruning deficits, and non-cell autonomous effects. Translational approaches target haplo-insufficient genes such as CHD8 and SCN2A using AAV or antisense oligonucleotides supported by isogenic iPSC models. Remaining challenges include model immaturity and scalability, while future directions focus on spatial perturb-omics, AI-driven causal inference, and standardized biobanks for precision ASD therapeutics.
1 September 2023 in Journal of Pure and Applied Microbiology