Advancing DNA nanopore technology towards clinical applications: Current status and future directions

Abstract

De novo designed nanopores capable of inserting into the cell membrane hold a remarkable potential for clinical applications, since they enable transmembrane transport of a wide variety of molecules into the cell. DNA nanotechnology serves as a well-established framework for developing these nanopores, as it offers immense design tunability with available modifications to ensure membrane insertion. This review gives a general overview of DNA nanopore developments, with the aim of offering a broader perspective on their prospects in clinical applications. The focus will be on different nanopore designs, multiple methods to facilitate lipid bilayer insertion, and various approaches for regulated transport. Moreover, potential advancements and research directions that may be required to translate DNA nanopores into clinical practice will be discussed. These include further development of approaches to target specific cell membranes, as well as investigating the immunogenicity and structural stability of DNA nanostructures in vivo. These developments could advance the field towards clinical implementation of DNA nanopores that are able to transport various molecules into specific cells in a controllable manner.