DNA hydrogel-based gene editing and drug delivery systems

Mo, Fangli; Jiang, Kai; Zhao, Di; Wang, Yuqi; Song, Jie; Tan, Weihong

doi:10.1016/j.addr.2020.07.018

Cited by 199 publications

(141 citation statements)

References 188 publications

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“…As an eminent skeleton material, DNA-based hydrogels have overcome a series of potential problems of targeted therapy systems because of their good biocompatibility, low toxicity, targeting, and other characteristics. It is believed that DNA-based hydrogels can be used as excellent drug carriers for the target treatment of many chronic diseases such as cancer in vivo ( Lattuada et al, 2020 ; Mo et al, 2021 ).…”

Section: Biomedical Application Of Dna-based Hydrogelsmentioning

confidence: 99%

Development, Preparation, and Biomedical Applications of DNA-Based Hydrogels

Jian

Luo

et al. 2021

Front. Bioeng. Biotechnol.

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Hydrogels have outstanding research and application prospects in the biomedical field. Among them, the design and preparation of biomedical hydrogels with deoxyribonucleic acid (DNA) as building blocks have attracted increasing research interest. DNA-based hydrogel not only has the skeleton function of hydrogel, but also retains its biological functions, including its excellent selection specificity, structural designability, precise molecular recognition ability, outstanding biocompatibility, and so on. It has shown important application prospects in the biomedical field, such as drug delivery, biosensing, and tissue engineering. In recent years, researchers have made full use of the characteristics of DNA molecules and constructed various pure DNA-based hydrogels with excellent properties through various crosslinking methods. Moreover, via introducing functional molecules or elements, or combining with other functional materials, a variety of multifunctional DNA-based hybrid hydrogels have also been constructed, which expand the breadth and depth of their applications. Here, we described the recent development trend in the area of DNA-based hydrogels and highlighted various preparation methods of DNA-based hydrogels. Representative biomedical applications are also exemplified to show the high performance of DNA-based hydrogels. Meanwhile, the existing problems and prospects are also summarized. This review provided references for the further development of DNA-based hydrogels.

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Section: Biomedical Application Of Dna-based Hydrogelsmentioning

confidence: 99%

Development, Preparation, and Biomedical Applications of DNA-Based Hydrogels

Jian

Luo

et al. 2021

Front. Bioeng. Biotechnol.

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“…Though pH-responsive DNA hydrogels have been reported elsewhere, they were mostly adopted for biosensing, bioimaging, and drug delivery. [31][32][33] Considering the complexity of mRNA, the use of pH-responsive DNA hydrogels to deliver mRNA has not yet been achieved. This method by adopting smart responsive DNA nano-hydrogel is expected to open up a new path for the delivery of functional mRNA in vivo, and has potential and huge application prospects in the field of disease treatment.…”

Section: Introductionmentioning

confidence: 99%

mRNA Delivery by a pH‐Responsive DNA Nano‐Hydrogel

Chen

Song

et al. 2021

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The delivery of mRNA to manipulate protein expression has attracted widespread attention, since that mRNA overcomes the problem of infection and mutation risks in transgenes and can work as drugs for the treatment of diseases. Although there are currently some vehicles that deliver mRNA into cells, they have not yet reached a good balance in terms of expression efficiency and biocompatibility. Here, a DNA nano‐hydrogel system for mRNA delivery is developed. The nano‐hydrogel is all composed of DNA except the target mRNA, so it has superior biocompatibility compared with those chemical vehicles. In parallel, the nano‐hydrogel can be compacted into a nanosphere under the crosslinking by well‐designed “X”‐shaped DNA scaffolds and DNA linkers, facilitating the delivery into cells through endocytosis. In addition, smart intracellular release of the mRNA is achieved by incorporating a pH‐responsive i‐motif structure into the nano‐hydrogel. Thus, taking the efficient delivery and release together, mRNA can be translated into the corresponding protein with a high efficiency, which is comparable to that of the commercial liposome but with a much better biocompatibility. Due to the excellent biocompatibility and efficiency, this nano‐hydrogel system is expected to become a competitive alternative for delivering functional mRNA in vivo.

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“…Additionally, the macroscopic properties of the material, such as the thermal sensitivity (Xing et al, 2011), pore size (Um et al, 2006), andviscosity (Fernandez-Castanon et al, 2018) can be tuned by the DNA sequences, which allows easy modification of the macroscopic properties of the material. Consequently, it is an ideal medium for gene editing (English et al, 2019), drug delivery systems (Mo et al, 2020), and sensors (Merindol et al, 2019). Similar to other hydrogels, their size affects the characterization of particles and might affect the delivery route or release of therapeutic agents (Mo et al, 2020), leading to the need for monodisperse DNA hydrogel particles.…”

Section: Introductionmentioning

confidence: 99%

“…Consequently, it is an ideal medium for gene editing (English et al, 2019), drug delivery systems (Mo et al, 2020), and sensors (Merindol et al, 2019). Similar to other hydrogels, their size affects the characterization of particles and might affect the delivery route or release of therapeutic agents (Mo et al, 2020), leading to the need for monodisperse DNA hydrogel particles.…”

Section: Introductionmentioning

confidence: 99%

Aqueous Triple-Phase System in Microwell Array for Generating Uniform-Sized DNA Hydrogel Particles

2021

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DNA hydrogels are notable for their biocompatibility and ability to incorporate DNA information and computing properties into self-assembled micrometric structures. These hydrogels are assembled by the thermal gelation of DNA motifs, a process which requires a high salt concentration and yields polydisperse hydrogel particles, thereby limiting their application and physicochemical characterization. In this study, we demonstrate that single, uniform DNA hydrogel particles can form inside aqueous/aqueous two-phase systems (ATPSs) assembled in a microwell array. In this process, uniform dextran droplets are formed in a microwell array inside a microfluidic device. The dextran droplets, which contain DNA motifs, are isolated from each other by an immiscible PEG solution containing magnesium ions and spermine, which enables the DNA hydrogel to undergo gelation. Upon thermal annealing of the device, we observed the formation of an aqueous triple-phase system in which uniform DNA hydrogel particles (the innermost aqueous phase) resided at the interface of the aqueous two-phase system of dextran and PEG. We expect ATPS microdroplet arrays to be used to manufacture other hydrogel microparticles and DNA/dextran/PEG aqueous triple-phase systems to serve as a highly parallel model for artificial cells and membraneless organelles.

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DNA hydrogel-based gene editing and drug delivery systems

Cited by 199 publications

References 188 publications

Development, Preparation, and Biomedical Applications of DNA-Based Hydrogels

Development, Preparation, and Biomedical Applications of DNA-Based Hydrogels

mRNA Delivery by a pH‐Responsive DNA Nano‐Hydrogel

Aqueous Triple-Phase System in Microwell Array for Generating Uniform-Sized DNA Hydrogel Particles

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