From Genomic Diagnosis to Personalized RNA Medicine: Advances in Next-Generation Sequencing and N-of-1 Antisense Oligonucleotide Therapies for Rare Genetic Diseases.
WHY IT MATTERS
This research shows a clear path for patients with rare genetic diseases to move from diagnosis to personalized treatment within a single medical framework, potentially reducing the diagnostic odyssey that currently takes years for many rare disease patients.
Scientists are getting better at finding rare genetic diseases using a tool called next-generation sequencing, which can read a person's DNA quickly and accurately. They're also developing new medicines called antisense oligonucleotides that can be customized for each patient to fix problems caused by genetic mutations. Together, these advances mean doctors can diagnose rare diseases faster and create personalized treatments tailored to each person's specific genetic makeup.
From Genomic Diagnosis to Personalized RNA Medicine: Advances in Next-Generation Sequencing and N-of-1 Antisense Oligonucleotide Therapies for Rare Genetic Diseases. Abstract: Next-generation sequencing (NGS) and antisense oligonucleotide (ASO) technologies are converging to transform the diagnosis and treatment of rare monogenic disorders. NGS enables comprehensive, single-test molecular diagnoses through targeted panels, whole-exome sequencing, and whole-genome sequencing, which together reveal pathogenic variants across coding, intronic, and structural domains. Integration with transcriptomic analyses, including RNA sequencing, further refines genotype-phenotype correlations and identifies splicing aberrations amenable to correction by ASOs. Therapeutic advances now span RNase H1-dependent gapmers for transcript knockdown, splice-modulating phosphorodiamidate morpholino oligomers (PMOs), and peptide/antibody-conjugated PMOs that enhance muscle and cardiac del Authors: Rodriguez Carstens et al. Journal: Genes MeSH: Humans, High-Throughput Nucleotide Sequencing, Precision Medicine, Oligonucleotides, Antisense, Rare Diseases, Genomics, Genetic Diseases, Inborn