DNA hydrogels are biocompatible drug delivery systems for targeted therapeutic interventions. Conventional DNA hydrogels, formed with many DNA nanostructure units, lead to increased preparation costs and design complexities. To address this, researchers from Japan constructed a Takumi-shaped DNA nanostructure with minimal DNA units and optimized its structure for improved in vivo retention abilities and sustained drug release. This study presents a promising DNA-based drug delivery system, which can potentially improve patient outcomes.
Hydrogels are polymeric materials with three-dimensional network structures containing large amounts of water. They serve as sustained-release drug delivery systems as they can encapsulate various bioactive substances, including drugs, antigens, and even cells. Hydrogels are better drug delivery alternatives than conventional systems, as they are more biocompatible, biodegradable, and easily administered as an injectable scaffold.
DNA has gained significant attention as a promising hydrogel material thanks to its customizable physicochemical properties, leading to the development of various DNA hydrogels. However, current methods like DNA ligase-linked hydrogels present many challenges, including potential allergic reactions and complex administration procedures that limit clinical applications.
Recently, a polypod-like nanostructured nucleic acid, or polypodna, was constructed using three or more predesigned oligodeoxynucleotides (ODNs) with partially complementary sequences to address these challenges. These efficient DNA nanostructures are easily injectable and readily reform into hydrogels at the injection site after being injected. While this approach creates self-gelatinizing nucleic acids that form hydrogels without DNA ligase, it requires multiple ODNs, leading to high preparation costs, design complexity, and an increased probability of off-target effects owing to the large number of DNA bases involved.
To address this, a Takumi-shaped DNA unit was formed with only two ODNs. However, studies investigating its optimization as a sustained-release drug carrier or its retention ability are limited.
In their new study, made available online on December 2, 2024, and to be published on January 10, 2025, in Volume 377 of the Journal of Controlled Release, Professor Makiya Nishikawa, along with Mr. Jian Jin, Assistant Professor Shoko Itakura, and Associate Professor Kosuke Kusamori, from the Tokyo University of Science, Japan, aimed to address these aspects of Takumi-shaped DNA nanostructures.
Prof. Nishikawa explained the motivation behind the study, "Our goal was to miniaturize and optimize DNA nanostructures so that stable DNA hydrogels could be formed with fewer nucleic acids."
Each ODN in the Takumi-shaped DNA structure was constructed with an eight-18 nucleotide-long palindromic stem attached to two cohesive parts on either side with a thymidine (T) spacer. The ODNs form a self-dimer via the palindromic sequence, and each ODN was named according to the number of nucleotides in the stem and cohesive parts. For instance, 14s-(T-10c)2 refers to an ODN with a stem length of 14 nucleotides and a cohesive part of 10 nucleotides located at both ends of the stem.
sources-science daily
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