WAI, Htoo A, Eliška SVOBODOVÁ, Natalia Romero HERRERA, Andrew G L DOUGLAS, John W HOLLOWAY, Francisco E BARALLE, Marco BARALLE and Diana BARALLE. Tailored antisense oligonucleotides designed to correct aberrant splicing reveal actionable groups of mutations for rare genetic disorders. EXPERIMENTAL AND MOLECULAR MEDICINE. LONDON: SPRINGERNATURE, 2024, 10 pp. ISSN 1226-3613. Available from: https://dx.doi.org/10.1038/s12276-024-01292-1.
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Basic information
Original name Tailored antisense oligonucleotides designed to correct aberrant splicing reveal actionable groups of mutations for rare genetic disorders
Authors WAI, Htoo A, Eliška SVOBODOVÁ, Natalia Romero HERRERA, Andrew G L DOUGLAS, John W HOLLOWAY, Francisco E BARALLE, Marco BARALLE and Diana BARALLE.
Edition EXPERIMENTAL AND MOLECULAR MEDICINE, LONDON, SPRINGERNATURE, 2024, 1226-3613.
Other information
Original language English
Type of outcome Article in a journal
Country of publisher United Kingdom of Great Britain and Northern Ireland
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 12.800 in 2022
Organization unit Faculty of Science
Doi http://dx.doi.org/10.1038/s12276-024-01292-1
UT WoS 001281876400004
Tags 14110114
Tags International impact, Reviewed
Changed by Changed by: Mgr. Tereza Miškechová, učo 341652. Changed: 9/9/2024 08:40.
Abstract
Effective translation of rare disease diagnosis knowledge into therapeutic applications is achievable within a reasonable timeframe; where mutations are amenable to current antisense oligonucleotide technology. In our study, we identified five distinct types of abnormal splice-causing mutations in patients with rare genetic disorders and developed a tailored antisense oligonucleotide for each mutation type using phosphorodiamidate morpholino oligomers with or without octa-guanidine dendrimers and 2 '-O-methoxyethyl phosphorothioate. We observed variations in treatment effects and efficiencies, influenced by both the chosen chemistry and the specific nature of the aberrant splicing patterns targeted for correction. Our study demonstrated the successful correction of all five different types of aberrant splicing. Our findings reveal that effective correction of aberrant splicing can depend on altering the chemical composition of oligonucleotides and suggest a fast, efficient, and feasible approach for developing personalized therapeutic interventions for genetic disorders within short time frames.
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