Knocking down gene expression: RNase H-mediated vs splice modulation of ITGA4

Antisense oligonucleotides are an emerging class of therapeutics that exert their effect via Watson-Crick base pairing to target mRNA and alter gene expressions. Here, we compared the efficacy of our steric blocking antisense oligonucleotides and an RNase H dependent drug currently in clinical trials, ATL1102, at knocking down integrin alpha 4 gene and protein expression. We also synthesized our steric blocking antisense oligonucleotides comprising various chemical modifications to identify the safest and most efficacious candidate. Generally, both mechanisms efficiently reduce the level of integrin alpha 4 protein production and cell surface expression. However, the steric blocking phosphorodiamidate morpholino oligomer and thiomorpholino recorded a greater reduction of integrin alpha 4 at lower doses with the ability to sustain the knockdown longer and exhibited fewer off-target effects compared to the ATL1102 RNase H dependent antisense oligonucleotide. Overall design: This dataset includes data from Jurkat cells treated with 2'-O-methoxyethyl modified nucleotides on a phosphorothioate backbone, MOE, phosphorodiamidate morpholino oligomers, PMOs, thiomorpholinos, TMOs, and Gapmer. Additionally, Jurkat cells treated with gene tool control, GTC, were included as control.