DNA Nanostructures: Current Challenges and Opportunities for Cellular Delivery

Abstract

DNA nanotechnology has produced a wide range of self-assembled structures, offering unmatched possibilities in terms of structural design. Because of their programmable assembly and precise control of size, shape, and function, DNA particles can be used for numerous biological applications, including imaging, sensing, and drug delivery. While the biocompatibility, programmability, and ease of synthesis of nucleic acids have rapidly made them attractive building blocks, many challenges remain to be addressed before using them in biological conditions. Enzymatic hydrolysis, low cellular uptake, immune cell recognition and degradation, and unclear biodistribution profiles are yet to be solved. Rigorous methodologies are needed to study, understand, and control the fate of self-assembled DNA structures in physiological conditions. In this review, we describe the current challenges faced by the field as well as recent successes, highlighting the potential to solve biology problems or develop smart drug delivery tools. We then propose an outlook to drive the translation of DNA constructs toward preclinical design. We particularly believe that a detailed understanding of the fate of DNA nanostructures within living organisms, achieved through thorough characterization, is the next required step to reach clinical maturity.

Nanobase.org: a repository for DNA and RNA nanostructures

“…We envision that a database like this will inspire comparative studies, both experimental as well as theoretical, across higher sample size of nanostructures. For example - dependence of properties such as serum stability ( 41 ), cell penetration efficiency ( 42 ), biodistribution ( 43 ) etc. can be studied over higher sample size with the help of a database like this.…”

Bioswitchable Delivery of microRNA by Framework Nucleic Acids: Application to Bone Regeneration

“…[27,47] In this study, we fabricated a tFNA-based bioswitchable delivery system that improves the miR transport efficiency in several ways. [48] First, the miRs were protected in the form of double-stranded RNA using antisense RNA hybridization. Second, the miRs were transported into cells dependent on the excellent cell-entrance ability of tFNA.…”

Innovative developments and emerging technologies in RNA therapeutics

“…However, more research efforts need to focus on the characterization of these constructs in physiological conditions to propel them towards clinical applications. The ongoing development of experimental methods to understand the fate of NA structures in terms of biodistribution, protein interactions, cellular uptake, and mechanisms of action represents a very promising strategy to achieve these goals and will facilitate the design of the next generation of constructs [ 168 ]. One outstanding challenge towards designing effective NA-based constructs for biological applications is the requirement for structures with improved resistance to enzymatic degradation [ 169 ].…”