AMOD is a web-based program that aids in the functional evaluation of nucleotide sequences through sequence characterization and antisense morpholino oligonucleotide (target site) selection. Submitted sequences are analyzed by translation initiation site prediction algorithms and sequence-to-sequence comparisons; results are used to characterize sequence features required for morpholino design. Within a defined subsequence, base composition and homodimerization values are computed for all putative morpholino oligonucleotides. Using these properties, morpholino candidates are selected and compared with genomic and transcriptome databases with the goal to identify target-specific enriched morpholinos. AMOD has been used at the University of Minnesota to design approximately 200 morpholinos for a functional genomics screen in zebrafish. The AMOD web server and a tutorial are freely available to both academic and commercial users at http://www.secretomes.umn.edu/AMOD/.
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http://dx.doi.org/10.1093/nar/gki453 | DOI Listing |
Cell Rep Med
December 2024
Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo 187-8502, Japan. Electronic address:
Duchenne muscular dystrophy (DMD) is a severe muscle disorder caused by mutations in the DMD gene, leading to dystrophin deficiency. Antisense oligonucleotide (ASO)-mediated exon skipping offers potential by partially restoring dystrophin, though current therapies remain mutation specific with limited efficacy. To overcome those limitations, we developed brogidirsen, a dual-targeting ASO composed of two directly connected 12-mer sequences targeting exon 44 using phosphorodiamidate morpholino oligomers.
View Article and Find Full Text PDFClin Genet
January 2025
Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Coxsackie and adenovirus receptor-like membrane protein (CLMP) mutation is identified as a genetic risk factor of congenital short bowel syndrome (CSBS). However, the specific pathogenic mechanism remains unclear. This study aimed to explore the clinical manifestations, genetic characteristics, and molecular mechanisms underlying CSBS caused by CLMP mutations.
View Article and Find Full Text PDFFront Immunol
December 2024
State Key Laboratory of Pathogen and Biosecurity, Beijing Academy of Military Medical Sciences, Beijing, China.
Introduction: Due to the impact of antibody-dependent enhancement and viral variation, effective vaccines or antiviral therapies remain lacking for the dengue virus (DENV). Nucleic acid drugs, particularly Vivo-Morpholinos (MOs), have emerged as a promising avenue for antiviral treatment due to their programmability and precise targeting, as well as their safety and stability.
Method: In this study, we designed and developed 10 morpho-modified (octa-guanidine dendrimer) vivo-MO molecules that target each coding gene of DENV.
Eur J Clin Invest
December 2024
Department of Surgery, University of California Los Angeles, Los Angeles, California, USA.
Background: Alternative splicing is a fundamental mechanism in the post-transcriptional regulation of genes. The multifunctional transmembrane glycoprotein receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) undergoes extensive alternative splicing to allow for tunable functions in cell signalling, adhesion and modulation of immune and metabolic responses. Splice isoforms that differ in their ectodomain and short or long cytoplasmic tail (CEACAM1-S/CEACAM1-L) have distinct functional roles.
View Article and Find Full Text PDFBlood Coagul Fibrinolysis
December 2024
Department of Biological Sciences, University of North Texas, Denton, Texas, USA.
Aim: This study aimed to create an f9l mutant zebrafish using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) and characterize its coagulation properties to investigate its functional similarity to human FX and explore the potential synergy between f9l and f10.
Methods: Three gRNAs targeting exon 8 encoded by the catalytic domain of the f9l gene were injected into 300 single-cell zebrafish embryos using CRISPR/Cas9 technology. DNA from the resulting adults was extracted from tail tips, and PCR was used to detect indels.
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