Investigation of twisted intercalating nucleic acid (TINA)-modified antisense oligonucleotides for splice modulation by induced exon-skipping in vitro

被引：21

作者：

Le, Bao T. ^{[1
,2
]}

Filichev, Vyacheslav V. ^{[3
]}

Veedu, Rakesh N. ^{[1
,2
]}

机构：

[1] Murdoch Univ, Ctr Comparat Genom, Perth, WA 6150, Australia

[2] Western Australian Neurosci Res Inst, Perth, WA 6150, Australia

[3] Massey Univ, Inst Fundamental Sci, Palmerston North 4442, New Zealand

来源：

RSC ADVANCES | 2016年 / 6卷 / 97期

关键词：

D O I：

10.1039/c6ra22346j

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Twisted intercalating nucleic acids (TINA)-modified oligonucleotides containing phenylethynylpyren-1-yl derivatives were reported to improve the thermal stability of the nucleic acid duplexes, triplexes and G-quadruplexes. In the present study, we have investigated the potential of TINA-modified antisense oligonucleotides (AOs) in splice modulation by induced exon-skipping in vitro. We used both para-TINA (p-TINA) and ortho-TINA (o-TINA)-modified 2'-O-methyl (2'-OMe) AOs on a phosphorothioate backbone (PS) designed to skip exon-23 in dystrophin pre-mRNA transcript in mdx mice myotubes. A fully-modified 2'-OMePS AO control was used in parallel. Our results showed that both p-TINA and o-TINA-modified AOs were able to induce exon-23 skipping. These results provide new insights on expanding the applicability of TINA-modified oligonucleotides.

引用

页码：95169 / 95172

页数：4

共 15 条

[1] Rational Design of Short Locked Nucleic Acid-Modified 2′-O-Methyl Antisense Oligonucleotides for Efficient Exon-Skipping In Vitro
Le, Bao T.
Adams, Abbie M.
Fletcher, Susan
Wilton, Stephen D.
Veedu, Rakesh N.
MOLECULAR THERAPY-NUCLEIC ACIDS, 2017, 9 : 155 - 161
[2] LOCKED NUCLEIC ACID-MODIFIED ANTISENSE OLIGONUCLEOTIDES FOR ENHANCED EXON SKIPPING IN DUCHENNE MUSCULAR DYSTROPHY
Veedu, Rakesh N.
Adams, Abbie
Fletcher, Sue
Shastri, Arun
Wengel, Jesper
Wilton, Steve
JOURNAL OF GENE MEDICINE, 2015, 17 (8-9): : 193 - 194
[3] Alpha-l-Locked Nucleic Acid-Modified Antisense Oligonucleotides Induce Efficient Splice Modulation In Vitro
Raguraman, Prithi
Wang, Tao
Ma, Lixia
Jorgensen, Per Trolle
Wengel, Jesper
Veedu, Rakesh N.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (07)
[4] Cationic polyelectrolyte-mediated delivery of antisense morpholino oligonucleotides for exon-skipping in vitro and in mdx mice
Wang, Mingxing
Wu, Bo
Tucker, Jason D.
Lu, Peijuan
Lu, Qilong
INTERNATIONAL JOURNAL OF NANOMEDICINE, 2015, 10 : 5635 - 5646
[5] Nucleobase-modified antisense oligonucleotides containing 5-(phenyltriazol)-2′-deoxyuridine nucleotides induce exon-skipping in vitro
Le, Bao T.
Hornum, Mick
Sharma, Pawan K.
Nielsen, Poul
Veedu, Rakesh N.
RSC ADVANCES, 2017, 7 (86): : 54542 - 54545
[6] Optimising efficacy of morpholino antisense oligonucleotide induced exon-skipping in vitro in the mdx mouse
McCulley, Caroline
Wells, Dominic
HUMAN GENE THERAPY, 2008, 19 (10) : 1175 - 1175
[7] Increasing the Analytical Sensitivity by Oligonucleotides Modified with Para- and Ortho-Twisted Intercalating Nucleic Acids - TINA
Schneider, Uffe V.
Geci, Imrich
Johnk, Nina
Mikkelsen, Nikolaj D.
Pedersen, Erik B.
Lisby, Gorm
PLOS ONE, 2011, 6 (06):
[8] Evaluation of anhydrohexitol nucleic acid, cyclohexenyl nucleic acid and D-altritol nucleic acid-modified 2′-O-methyl RNA mixmer antisense oligonucleotides for exon skipping in vitro
Le, Bao T.
Chen, Suxiang
Abramov, Mikhail
Herdewijn, Piet
Veedu, Rakesh N.
CHEMICAL COMMUNICATIONS, 2016, 52 (92) : 13467 - 13470
[9] Levels of Exon-Skipping Are Not Artificially Overestimated Because of the Increased Affinity of Tricyclo-DNA-Modified Antisense Oligonucleotides to the Target DMD Exon
Doisy, Mathilde
Vacca, Ophelie
Saoudi, Amel
Goyenvalle, Aurelie
NUCLEIC ACID THERAPEUTICS, 2024, 34 (05) : 214 - 220
[10] Effective exon skipping and restoration of dystrophin expression by peptide nucleic acid antisense oligonucleotides in mdx mice
Yin, Haifang
Lu, Qilong
Wood, Matthew
MOLECULAR THERAPY, 2008, 16 (01) : 38 - 45

← 1 2 →