Tagged DNA nanotubes used to stimulate a targeted immune response in vivo
Researchers from Ludwig Maximilians University of Munich have used microinjection of unmethylated CpG sequences, carried by DNA nanotubes, to elicit an innate immune response in localised tissues of anesthetised mice.
Their results suggest that DNA nanotubes could be useful tools for creating targeted macrophage activation in tissues to produce localised immune system activation.
This offers significant advantages over traditional therapies used to boost the immune response as conventional drugs normally act non-specifically and systematically. They can also have serious side effects and antimicrobial drugs used to help fight viral and bacterial infections often lead to drug-resistant pathogens.
Targeted delivery of drugs or stimulation of the immune system aims to reduce the unwanted reactions of these treatments.
DNA structures as a method of achieving this have a number of benefits:
- They can be modified through many different processes with nanoscale precision
- They aren't cytotoxic
- They can survive in cell media, blood serum and cultured cells
- They can carry immune-stimulatory motifs
Unmethylated CpG sequences are known to have immunogenic properties and are often used as adjuvants in vaccinations or to treat tumour-associated immunosuppression. They are recognised by the Toll-like receptor 9 (TLR9) in the endosome of innate immune system cells and cause the production and secretion of inflammatory moderators.
In this study, led by Markus Rehberg, the researchers showed that the CpG labelled DNA nanotubes were quickly localised in the endolysosomal system of tissue macrophages after microinjection. This initiated an inflammatory response and significantly increased leukocyte rolling and transmigration into the tissue.
When unlabelled DNA nanotubes or just CpG sequences were microinjected there was no significant localised immune response. This is encouraging for further research in the use of DNA nanotubes to target macrophages in vivo with a number of potential applications.
Localised microinjection of the DNA nanotubes was carried out using a PatchStar motorised micromanipulator.
Sellner S, Kocabey S, Nekolla K, Krombach F, Liedl T, Rehberg M DNA nanotubes as intracellular delivery vehicles in vivo Biomaterials 53, 453-463 (2015) doi: 10.1016/j.biomaterials.2015.02.099
Featured image: Micrograph of leukocyte migration with H&E staining