Estimated number of off-target candidate sites for antisense oligonucleotides in human mRNA sequences.
Genes Cells
; 23(6): 448-455, 2018 Jun.
Article
em En
| MEDLINE
| ID: mdl-29667281
ABSTRACT
Antisense oligonucleotide (ASO) therapeutics are single-stranded oligonucleotides which bind to RNA through sequence-specific Watson-Crick base pairings. A unique mechanism of toxicity for ASOs is hybridization-dependent off-target effects that can potentially occur due to the binding of ASOs to complementary regions of unintended RNAs. To reduce the off-target effects of ASOs, it would be useful to know the approximate number of complementary regions of ASOs, or off-target candidate sites of ASOs, of a given oligonucleotide length and complementarity with their target RNAs. However, the theoretical number of complementary regions with mismatches has not been reported to date. In this study, we estimated the general number of complementary regions of ASOs with mismatches in human mRNA sequences by mathematical calculation and in silico analysis using several thousand hypothetical ASOs. By comparing the theoretical number of complementary regions estimated by mathematical calculation to the actual number obtained by in silico analysis, we found that the number of complementary regions of ASOs could be broadly estimated by the theoretical number calculated mathematically. Our analysis showed that the number of complementary regions increases dramatically as the number of tolerated mismatches increases, highlighting the need for expression analysis of such genes to assess the safety of ASOs.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
/
Genoma Humano
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Oligonucleotídeos Antissenso
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Marcação de Genes
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article