Tailored antisense oligonucleotides designed to correct
aberrant splicing reveal actionable groups of mutations for
rare genetic disorders

J 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, SPRINGER NATURE, 2024, 1226-3613

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 12.900

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/24:00137052

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

Antisense oligonucleotides; Aberrant splicing correction; Rare genetic disorders; Precision medicine; Targeted gene therapy

Štítky

14110114, 14314010, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 27. 8. 2025 09:25, Mgr. Marie Novosadová Šípková, DiS.

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.

Citovat

WAI, Htoo A; Eliška SVOBODOVÁ; Natalia Romero HERRERA; Andrew G L DOUGLAS; John W HOLLOWAY; Francisco E BARALLE; Marco BARALLE a Diana BARALLE. Tailored antisense oligonucleotides designed to correct aberrant splicing reveal actionable groups of mutations for rare genetic disorders. EXPERIMENTAL AND MOLECULAR MEDICINE. LONDON: SPRINGER NATURE, 2024, roč. 56, č. 8, s. 1816-1825. ISSN 1226-3613. Dostupné z: https://doi.org/10.1038/s12276-024-01292-1.

@article{2430477,
   author = {Wai, Htoo A and Svobodová, Eliška and Herrera, Natalia Romero and Douglas, Andrew G L and Holloway, John W and Baralle, Francisco E and Baralle, Marco and Baralle, Diana},
   article_location = {LONDON},
   article_number = {8},
   doi = {https://doi.org/10.1038/s12276-024-01292-1},
   keywords = {Antisense oligonucleotides; Aberrant splicing correction; Rare genetic disorders; Precision medicine; Targeted gene therapy},
   language = {eng},
   issn = {1226-3613},
   journal = {EXPERIMENTAL AND MOLECULAR MEDICINE},
   title = {Tailored antisense oligonucleotides designed to correct aberrant splicing reveal actionable groups of mutations for rare genetic disorders},
   url = {https://www.nature.com/articles/s12276-024-01292-1},
   volume = {56},
   year = {2024}
}

TY  - JOUR
ID  - 2430477
AU  - Wai, Htoo A - Svobodová, Eliška - Herrera, Natalia Romero - Douglas, Andrew G L - Holloway, John W - Baralle, Francisco E - Baralle, Marco - Baralle, Diana
PY  - 2024
TI  - Tailored antisense oligonucleotides designed to correct aberrant splicing reveal actionable groups of mutations for rare genetic disorders
JF  - EXPERIMENTAL AND MOLECULAR MEDICINE
VL  - 56
IS  - 8
SP  - 1816-1825
EP  - 1816-1825
PB  - SPRINGER NATURE
SN  - 12263613
KW  - Antisense oligonucleotides
KW  - Aberrant splicing correction
KW  - Rare genetic disorders
KW  - Precision medicine
KW  - Targeted gene therapy
UR  - https://www.nature.com/articles/s12276-024-01292-1
N2  - 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.
ER  -

WAI, Htoo A; Eliška SVOBODOVÁ; Natalia Romero HERRERA; Andrew G L DOUGLAS; John W HOLLOWAY; Francisco E BARALLE; Marco BARALLE a Diana BARALLE. Tailored antisense oligonucleotides designed to correct aberrant splicing reveal actionable groups of mutations for rare genetic disorders. \textit{EXPERIMENTAL AND MOLECULAR MEDICINE}. LONDON: SPRINGER NATURE, 2024, roč.~56, č.~8, s.~1816-1825. ISSN~1226-3613. Dostupné z: https://doi.org/10.1038/s12276-024-01292-1.

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