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.

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

Language

English

Type of outcome

Článek v odborném periodiku

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

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

Abstract

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 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.

@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},
   doi = {http://dx.doi.org/10.1038/s12276-024-01292-1},
   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},
   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
PB  - SPRINGERNATURE
SN  - 12263613
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 and 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: SPRINGERNATURE, 2024, 10 pp. ISSN~1226-3613. Available from: https://dx.doi.org/10.1038/s12276-024-01292-1.

Detailed Information on Publication Record