We chose to first test AZD9150 in the A431 subcutaneous human epidermoid tumor xenograft model because A431 cells were among the cells most sensitive to ASO under free uptake conditions in vitro (IC 50 11 nmol/L) and because the depletion of STAT3 did not result in inhibition of A431 cell proliferation . Thus, effects on STAT3 in this tumor ...

2015年11月18日 · We describe the preclinical activity and initial clinical evaluation of a class of ASOs containing constrained ethyl modifications for targeting the gene encoding the transcription factor STAT3, a notoriously difficult protein to inhibit therapeutically.

2017年2月27日 · Antisense oligonucleotides (ASOs) modified with phosphorothioate (PS) linkages and different 2′ modifications can be used either as drugs (e.g., to treat homozygous...

2023年6月13日 · McMahon and colleagues use a CRISPR-Cas gene activation screen to identify GOLGA8N as a gene that can enhance bulk antisense oligonucleotide uptake and increase activity of both splice-switching and RNase H1-activating ASOs in cell lines initially poor at productive ASO uptake.

2021年11月1日 · Next generation modified antisense oligonucleotides (ASOs) are commercially approved new therapeutic modalities, yet poor productive uptake and endosomal entrapment in tumour cells limit...

2018年4月4日 · Uptake of PS-ASOs through EGFR results in increased PS-ASO activities in A431 cells, suggesting that EGFR facilitates PS-ASO sorting into compartments with more efficient release than other receptors/pathways.

2024年4月11日 · The therapeutic potential of a THOC7-AS1 antisense oligonucleotide (ASO) was assessed in cSCC, employing a designed ASO targeting THOC7-AS1 (Fig. 7A). In A431 cells, treatment with the THOC7-AS1 ASO resulted in a dose-dependent reduction of THOC7-AS1 expression, with optimal inhibition observed at 8 µM (Fig. 7 B).

2022年12月1日 · Using A431 cells, Wang et al. determined that PS-ASOs were trafficked together with EGF in clathrin-coated vesicles (Wang et al., 2018). A431 cells have an abnormally high expression of EGFR, which likely dominates receptor-mediated endocytosis in this cell type.

In this experiment, free uptake of FAM-B-ASO was monitored in A431 cancer cells exhibiting high EGFR expression levels compared to NHDFs with low EGFR density. Cells were treated with FAM-B-ASO (80 pmol/well) and after 12 h of incubation, cells were visualized by green fluorescence microscopy (Figure 3D). In parallel, the nuclei of the tested ...

2022年11月26日 · Antisense reduction of EGFR in A431 and U87-MG cells resulted in decreased boron accumulation compared to control cells, indicating that cellular uptake of B-ASOs is related to EGFR-dependent internalization.