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- Title
Template-Assisted Assembly of Hybrid DNA/RNA Nanostructures Using Branched Oligodeoxy- and Oligoribonucleotides.
- Authors
Fokina, Alesya; Poletaeva, Yulia; Dukova, Svetlana; Klabenkova, Kristina; Rad'kova, Zinaida; Bakulina, Anastasia; Zatsepin, Timofei; Ryabchikova, Elena; Stetsenko, Dmitry
- Abstract
A template-assisted assembly approach to a C24 fullerene-like double-stranded DNA polyhedral shell is proposed. The assembly employed a supramolecular oligonucleotide dendrimer as a 3D template that was obtained via the hybridization of siRNA strands and a single-stranded DNA oligonucleotide joined to three- or four-way branched junctions. A four-way branched oligonucleotide building block (a starlet) was designed for the assembly of the shell composed of three identical self-complementary DNA single strands and a single RNA strand for hybridization to the DNA oligonucleotides of the template. To prevent premature auto-hybridization of the self-complementary oligonucleotides in the starlet, a photolabile protecting group was introduced via the N3-substituted thymidine phosphoramidite. Cleavable linkers such as a disulfide linkage, RNase A sensitive triribonucleotides, and di- and trideoxynucleotides were incorporated into the starlet and template at specific points to guide the post-assembly disconnection of the shell from the template, and enzymatic disassembly of the template and the shell in biological media. At the same time, siRNA strands were modified with 2′-OMe ribonucleotides and phosphorothioate groups in certain positions to stabilize toward enzymatic digestion. We report herein a solid-phase synthesis of branched oligodeoxy and oligoribonucleotide building blocks for the DNA/RNA dendritic template and the branched DNA starlet for a template-assisted construction of a C24 fullerene-like DNA shell after initial molecular modeling, followed by the assembly of the shell around the DNA-coated RNA dendritic template, and visualization of the resulting nanostructure by transmission electron microscopy.
- Subjects
NUCLEIC acid hybridization; RNA; DNA; OLIGONUCLEOTIDES; FULLERENE polymers; SOLID-phase synthesis; HOLLIDAY junctions; MESSENGER RNA; SINGLE-stranded DNA
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 21, p15978
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms242115978