October 2017 Paper of the Month

Nucleic acid binding proteins affect the subcellular distribution of phosphorothioate antisense oligonucleotides

Bailey JK, Shen W, Liang XH, Crooke ST. Nucleic Acids Res. 2017 Oct 13;45(18):10649-10671. This paper is the latest in a series of publications from Stanley Crooke’s lab at Ionis investigating the interactions between phosphorothioate antisense oligonucleotides and intracellular proteins. The lab has previously identified over 50 intracellular proteins that bind PS-ASOs and shown that…

Folate – the new kid on the block of oligonucleotide conjugates for targeted delivery?

According to a new paper by Orellana et al.1 this may well be the case. The paper mainly focuses on a folate-conjugated microRNA 34a mimic for the treatment of cancer, but a folate-conjugated Luc siRNA was also successfully delivered to and active in cells expressing the folate receptor (FOLR1). The FOLR1 ligand folate (vitamin B9)…

nucleic acid immunity

Nucleic acid immunity as relevant to oligonucleotide therapeutics

Under the constant selection pressure of infection by diverse and ever-changing pathogens, eukaryotic cells and organisms have evolved complex immune systems to defend themselves. Of particular interest for the oligonucleotide therapeutics field is the response of the innate immune system to the introduction of exogenous nucleic acids and how to bypass or manipulate this reaction…