Tissue-specific targeting of DNA nanodevices in a multicellular living organism.

Kasturi Chakraborty,Sandhya P Koushika,Sunaina Surana,Paschalis Kratsios,Sandrine Moutel,Yamuna Krishnan,Jihad Aburas,Palapuravan Anees,Simona Martin,Franck Perez

doi:10.7554/elife.67830

Abstract

Nucleic acid nanodevices present great potential as agents for logic-based therapeutic intervention as well as in basic biology. Often, however, the disease targets that need corrective action are localized in specific organs, and thus realizing the full potential of DNA nanodevices also requires ways to target them to specific cell types in vivo. Here, we show that by exploiting either endogenous or synthetic receptor-ligand interactions and leveraging the biological barriers presented by the organism, we can target extraneously introduced DNA nanodevices to specific cell types in Caenorhabditis elegans, with subcellular precision. The amenability of DNA nanostructures to tissue-specific targeting in vivo significantly expands their utility in biomedical applications and discovery biology.

Highlights

DNA has proven to be a versatile molecular scaffold to build an array of programmable synthetic nanoarchitectures due to its structural predictability(Seeman & Sleiman, 2017)
The intestine is one of the major organs of C. elegans, comprising a third of the total somatic mass with twenty large epithelial cells positioned with bilateral symmetry, forming a long tube around a lumen(McGhee, contain prominent, birefringent gut granules that are known as lysosome-related organelles (LROs)
We reasoned that the biological barrier between the intestinal lumen and the pseudocoelom would effectively preclude D38 from access to coelomocytes, as seen whenever DNA nanodevices are microinjected in the pseudocoelom(Bhatia, Surana, Chakraborty, Koushika, & Krishnan, 2011; Surana et al, 2011)

Summary

Introduction

DNA has proven to be a versatile molecular scaffold to build an array of programmable synthetic nanoarchitectures due to its structural predictability(Seeman & Sleiman, 2017). We demonstrate that DNA nanodevices can be targeted tissuespecifically in the nematode C. elegans by leveraging both natural and synthetic receptors, on the surface of different cell types. When 9E is fused to the synaptic vesicle protein synaptobrevin-1 (SNB-1) and selectively expressed in neurons, the SNB-1::9E chimera binds DNA nanodevices having the cognate 4-nt domain and localizes them in retrogradelymoving endosomes in neurons (Figure 1c).

Results

Conclusion