Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 12, Issue 50, Pages 55554-55563Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.0c12506
Keywords
DNA-RNA hybrid hydrogel; dual polymerization; siRNA-aptamer complex; self-assembly; injectable hydrogel
Funding
- Bio & Medical Technology Development Program of the National Research Foundation of Korea (NRF) - Korean Government [NRF-2016M3A9C6917402]
- Creative Materials Discovery Program through the National Research Foundation of Korea (NRF) - Ministry of Science and ICT (MSIT) [NRF-2017M3D1A1039423]
- NRF - MSIT [NRF-2017R1E1A1A01075027]
- National Research Foundation of Korea [4299990414506] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Advances in the DNA nanotechnology have enabled the fabrication of DNA-based hydrogels with precisely controlled structures and tunable mechanical and biological properties. Compared to DNA hydrogel, preparation of RNA-based hydrogel remains challenging due to the inherent instability of naked RNA. To overcome these limitations, we fabricated a DNA-RNA hybrid hydrogel via stepwise dual enzymatic polymerization. Multimeric short hairpin RNAs (shRNAs) were hybridized with functional DNA aptamers for targeting and mechanical properties of the hydrogel. The obtained DNA-RNA hybrid hydrogel was ultrasoft, robust, and injectable hence reconfigurable into any confined structures. As a model system, the hydrogel was able to mimic microtubule structures under physiological conditions and designed to release the functional small interfering RNA (siRNA)-aptamer complex (SAC) sequentially. In addition, we encoded restriction enzyme-responsive sites in DNA-RNA hybrid hydrogel to boost the release of SAC. This novel strategy provides an excellent platform for systematic RNA delivery through double-controlled release, SAC release from hydrogel, and subsequent release of siRNA from the SAC, which has promising potential in RNA therapy.
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