Selecting Therapeutic Antisense Oligonucleotides with Gene Targeting and TLR8 Potentiating Bifunctionality.
Methods Mol Biol
; 2691: 225-234, 2023.
Article
em En
| MEDLINE
| ID: mdl-37355549
ABSTRACT
A growing body of preclinical evidence has led to the hypothesis that human Toll-like receptor 8 (hTLR8) activation in the tumor microenvironment (TME) could have potent anticancer effects through its action on monocytes, myeloid dendritic cells (mDCs), and natural killer (NK) cells. This has motivated the initiation of several clinical trials for chemical hTLR8 agonists in a variety of cancers. Concurrently, a growing number of synthetic antisense oligonucleotides (ASOs) are being developed as cancer therapeutics. We have recently reported that 2'-O-methyl (2'OMe)-modified ASOs can potentiate sensing of hTLR8 chemical agonists in a sequence-dependent manner. This suggests that select gene-targeting ASOs with anticancer activity may synergize with low-dose hTLR8 agonists in the TME. Here, we provide a detailed protocol to rapidly screen and identify such synthetic bifunctional oligonucleotides with synergistic activity on hTLR8 sensing.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Oligonucleotídeos Antissenso
/
Receptor 8 Toll-Like
Tipo de estudo:
Guideline
Limite:
Humans
Idioma:
En
Revista:
Methods Mol Biol
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Austrália