A Non-Coding Oligonucleotide Recruits Cutaneous CD11b Cells that Inhibit Thelper Responses and Promote Tregs.

Skin-resident antigen-presenting cells (APC) play an important role in maintaining peripheral tolerance via immune checkpoint proteins and induction of T regulatory cells (Tregs). However, there is a lack of knowledge on how to expand or recruit immunoregulatory cutaneous cells without causing inflammation. Here, it is shown that administration of a non-coding single-stranded oligonucleotide (ssON) leads to CCR2-dependent accumulation of CD45CD11bLy6C cells in the skin that express substantial levels of PD-L1 and ILT3.

Synergistic antiviral activity against drug-resistant HIV-1 by naturally occurring dipeptide and A single-stranded oligonucleotide.

The novel dipeptide WG-am and single-stranded oligonucleotide combination (WG-am:ssON) showed synergistic antiviral activity against HIV-1 integrase-, protease- or reverse transcriptase drug resistant isolates, with over 95% reduction. The highest selectivity indexes were for integrase resistant isolates. WG-am:ssON can be a future option for treatment of HIV drug-resistant strains.

Is There a Role for Immunoregulatory and Antiviral Oligonucleotides Acting in the Extracellular Space? A Review and Hypothesis.

Here, we link approved and emerging nucleic acid-based therapies with the expanding universe of small non-coding RNAs (sncRNAs) and the innate immune responses that sense oligonucleotides taken up into endosomes. The Toll-like receptors (TLRs) 3, 7, 8, and 9 are located in endosomes and can detect nucleic acids taken up through endocytic routes. These receptors are key triggers in the defense against viruses and/or bacterial infections, yet they also constitute an Achilles heel towards the discrimination between self- and pathogenic nucleic acids.

Inhibition of Respiratory Syncytial Virus Infection by Small Non-Coding RNA Fragments.

Respiratory syncytial virus (RSV) causes acute lower respiratory tract infection in infants, immunocompromised individuals and the elderly. As the only current specific treatment options for RSV are monoclonal antibodies, there is a need for efficacious antiviral treatments against RSV to be developed. We have previously shown that a group of synthetic non-coding single-stranded DNA oligonucleotides with lengths of 25-40 nucleotides can inhibit RSV infection in vitro and in vivo.