Limited premature termination codon suppression by read-through agents in cystic fibrosis intestinal organoids

D. D. Zomer-van Ommen; L. A.W. Vijftigschild; E. Kruisselbrink; A. M. Vonk; J. F. Dekkers; H. M. Janssens; K. M. de Winter-de Groot; C. K. van der Ent; J. M. Beekman

doi:10.1016/j.jcf.2015.07.007

Limited premature termination codon suppression by read-through agents in cystic fibrosis intestinal organoids

D. D. Zomer-van Ommen
, L. A.W. Vijftigschild
, E. Kruisselbrink
, A. M. Vonk
, J. F. Dekkers
, H. M. Janssens
, K. M. de Winter-de Groot
, C. K. van der Ent
, J. M. Beekman

Research output: Contribution to journal › Article › peer-review

45 Citations (Scopus)

Abstract

Premature termination codon read-through drugs offer opportunities for treatment of multiple rare genetic diseases including cystic fibrosis. We here analyzed the read-through efficacy of PTC124 and G418 using human cystic fibrosis intestinal organoids (E60X/4015delATTT, E60X/F508del, G542X/F508del, R1162X/F508del, W1282X/F508del and F508del/F508del). G418-mediated read-through induced only limited CFTR function, but functional restoration of CFTR by PTC124 could not be confirmed. These studies suggest that better read-through agents are needed for robust treatment of nonsense mutations in cystic fibrosis.

Original language	English
Pages (from-to)	158-162
Number of pages	5
Journal	Journal of Cystic Fibrosis
Volume	15
Issue number	2
DOIs	https://doi.org/10.1016/j.jcf.2015.07.007
Publication status	Published - 1 Mar 2016
Externally published	Yes

Keywords

Cystic fibrosis
G418
Intestinal organoids
Nonsense suppression
PTC124
Read-through

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10.1016/j.jcf.2015.07.007

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Zomer-van Ommen, D. D., Vijftigschild, L. A. W., Kruisselbrink, E., Vonk, A. M., Dekkers, J. F., Janssens, H. M., de Winter-de Groot, K. M., van der Ent, C. K., & Beekman, J. M. (2016). Limited premature termination codon suppression by read-through agents in cystic fibrosis intestinal organoids. Journal of Cystic Fibrosis, 15(2), 158-162. https://doi.org/10.1016/j.jcf.2015.07.007

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title = "Limited premature termination codon suppression by read-through agents in cystic fibrosis intestinal organoids",

abstract = "Premature termination codon read-through drugs offer opportunities for treatment of multiple rare genetic diseases including cystic fibrosis. We here analyzed the read-through efficacy of PTC124 and G418 using human cystic fibrosis intestinal organoids (E60X/4015delATTT, E60X/F508del, G542X/F508del, R1162X/F508del, W1282X/F508del and F508del/F508del). G418-mediated read-through induced only limited CFTR function, but functional restoration of CFTR by PTC124 could not be confirmed. These studies suggest that better read-through agents are needed for robust treatment of nonsense mutations in cystic fibrosis.",

keywords = "Cystic fibrosis, G418, Intestinal organoids, Nonsense suppression, PTC124, Read-through",

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note = "Publisher Copyright: {\textcopyright} 2015 European Cystic Fibrosis Society.",

year = "2016",

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doi = "10.1016/j.jcf.2015.07.007",

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AU - Zomer-van Ommen, D. D.

AU - Vijftigschild, L. A.W.

AU - Kruisselbrink, E.

AU - Vonk, A. M.

AU - Dekkers, J. F.

AU - Janssens, H. M.

AU - de Winter-de Groot, K. M.

AU - van der Ent, C. K.

AU - Beekman, J. M.

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N2 - Premature termination codon read-through drugs offer opportunities for treatment of multiple rare genetic diseases including cystic fibrosis. We here analyzed the read-through efficacy of PTC124 and G418 using human cystic fibrosis intestinal organoids (E60X/4015delATTT, E60X/F508del, G542X/F508del, R1162X/F508del, W1282X/F508del and F508del/F508del). G418-mediated read-through induced only limited CFTR function, but functional restoration of CFTR by PTC124 could not be confirmed. These studies suggest that better read-through agents are needed for robust treatment of nonsense mutations in cystic fibrosis.

AB - Premature termination codon read-through drugs offer opportunities for treatment of multiple rare genetic diseases including cystic fibrosis. We here analyzed the read-through efficacy of PTC124 and G418 using human cystic fibrosis intestinal organoids (E60X/4015delATTT, E60X/F508del, G542X/F508del, R1162X/F508del, W1282X/F508del and F508del/F508del). G418-mediated read-through induced only limited CFTR function, but functional restoration of CFTR by PTC124 could not be confirmed. These studies suggest that better read-through agents are needed for robust treatment of nonsense mutations in cystic fibrosis.

KW - Cystic fibrosis

KW - G418

KW - Intestinal organoids

KW - Nonsense suppression

KW - PTC124

KW - Read-through

UR - https://www.scopus.com/pages/publications/84938629987

U2 - 10.1016/j.jcf.2015.07.007

DO - 10.1016/j.jcf.2015.07.007

M3 - Article

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SN - 1569-1993

VL - 15

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EP - 162

JO - Journal of Cystic Fibrosis

JF - Journal of Cystic Fibrosis

IS - 2

ER -

Limited premature termination codon suppression by read-through agents in cystic fibrosis intestinal organoids

Abstract

Keywords

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