Rna nanostructures, methods of making, and uses thereof
AssigneeUniversity of Kentucky Research Foundation
InventorsPeixuan Guo, Mario Vieweger, Xin Li, Sijin Guo, Hongran Yin, Xijun Piao
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Abstract
Disclosed herein are high Tm RNA nanostructures that can be composed of one or more modules or motifs to build RNA nanostructures with or without layers. The RNA nanostructures can have a core domain and three or more double-stranded arms and formulations thereof to conjugate high copy numbers of therapeutics, pH responsive or enzyme cleavable drug cargo. Also described herein is a design strategy for generation of synthetic RNA oligonucleotides that can self assemble into highly thermostable RNA structures. Also described herein are uses of the RNA nanostructures described herein.
Claims28
A modular RNA motif comprising:
- at least three synthetic RNA oligonucleotides, wherein the at least three synthetic RNA oligonucleotides are coupled to each other, wherein the at least three synthetic RNA oligonucleotides form a central core domain and at least three double-stranded arms arranged around the core domain and extending away from the central core domain, wherein the melting temperature of the RNA motif is greater than 65 degrees Celcius, wherein the at least three synthetic RNA oligonucleotides are configured to self-assemble to form the modular RNA motif.
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A system, comprising:
- a computing device;
- and
- an application executable on the computing device, wherein when executed, the application causes the computing device to at least:
- generate theoretical double-stranded arm (DA) sequences based at least in part on the GC content of the theoretical DA sequence, melting temperature (Tm) of the theoretical DA sequence, and ability to self-dimerize;
- select one or more DA(s) for a set of oligomers based at least in part on a computed cross complementarity of a saved set of DAs, wherein DAs having the lowest overall complementarity are selected;
- computes oligomer sequences, which comprises computing the reverse complement of DA sequences, computing extension oligomer sequences, and computing termination oligomer sequences;
- and
- select oligomers based at least in part on the ability of the oligomers to self-dimerize or form dimers, wherein those oligomers that do not self-dimerize and do not form dimers are selected.
A method comprising:
- generating theoretical double-stranded arm (DA) sequences based at least in part on the GC content of the theoretical DA sequence, melting temperature (Tm) of the theoretical DA sequence, and ability to self-dimerize;
- selecting one or more DA(s) for a set of oligomers based at least in part on a computed cross complementarity of a saved set of DAs, wherein DAs having the lowest overall complementarity are selected;
- computing oligomer sequences, which comprises computing the reverse complement of DA sequences, computing extension oligomer sequences, and computing termination oligomer sequences;
- and
- selecting oligomers based at least in part on the ability of the oligomers to self-dimerize or form dimers, wherein those oligomers that do not self-dimerize and do not form dimers are selected.
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Dependencies are inferred from the claim text.