2024
Tailored antisense oligonucleotides designed to correct aberrant splicing reveal actionable groups of mutations for rare genetic disorders
WAI, Htoo A, Eliška SVOBODOVÁ, Natalia Romero HERRERA, Andrew G L DOUGLAS, John W HOLLOWAY et. al.Základní údaje
Originální název
Tailored antisense oligonucleotides designed to correct aberrant splicing reveal actionable groups of mutations for rare genetic disorders
Autoři
WAI, Htoo A, Eliška SVOBODOVÁ, Natalia Romero HERRERA, Andrew G L DOUGLAS, John W HOLLOWAY, Francisco E BARALLE, Marco BARALLE a Diana BARALLE
Vydání
EXPERIMENTAL AND MOLECULAR MEDICINE, LONDON, SPRINGERNATURE, 2024, 1226-3613
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Stát vydavatele
Velká Británie a Severní Irsko
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 12.800 v roce 2022
Organizační jednotka
Přírodovědecká fakulta
UT WoS
001281876400004
Štítky
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 9. 9. 2024 08:40, Mgr. Tereza Miškechová
Anotace
V originále
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.