Prna mutlivalent junction domain for use in stable multivalent rna nanoparticles
AssigneeUniversity of Cincinnati
InventorPeixuan Guo
Life of this patent
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Abstract
Trifurcate RNA junction domains derived from phi29 pRNA are described that assemble with high affinity and that are stable in vitro and in vivo. Further expansion of trifurcated RNA domains to multiple way junction scaffolds via creative designs enable an array of toolkit to construct nanoparticle architectures with diverse shapes and angles. The scaffolds can be used to form RNA nanoparticles having a wide variety of uses, including promotion of RNA crystallization, creation of RNA aptamer with high affinity to mimic antibody, delivery of therapeutic and/or diagnostic agents such as biologically active RNA-based moieties, including siRNA, ribozymes, aptamers, and others.
Claims38
A multivalent RNA junction scaffold, comprising:
- a multiple RNA oligomer-formed polymer complex, wherein said polymer complex is configured to promote an array of thermodynamically and stoichiometrically stable RNA nanoparticles.
A multipartite RNA nanoparticle, comprising an array of thermodynamically and stoichiometrically stable, multifunctional bioactive moiety crystalline, wherein said crystalline is self-assembled by a multivalent RNA junction scaffold, wherein said multivalent RNA junction scaffold is a multiple RNA oligomer formed polymer complex.
A method of making a multipartite RNA nanoparticle, comprising admixing in substantially equimolar amounts of RNA polynucleotides, wherein said RNA polynucleotides contain a collection of RNA junction domains to form a multivalent RNA junction scaffold and promote the assembly of an array of bioactive moiety into crystalline structure.
A method of delivering a biological active moiety to a cell, comprising contacting the cell with a multipartite RNA nanoparticle, wherein said multipartite RNA nanoparticle is assembled by an RNA junction scaffold.
A method of delivering a therapeutic agent or a detectable labeling agent, or both, comprising administering to the subject a multipartite RNA nanoparticle, wherein said multipartite RNA nanoparticle is assembled by an RNA junction scaffold.
A method of using trifurcate or four way X-motif junction domain as a scaffold to produce stable multivalent RNA aptamers, wherein said stable multivalent RNA aptamers recognize at least one given substrate, comprising:
- a. attaching a collection of random sequences to pRNA trifurcate or four way X-motif junction domain;
- b. selecting said random sequences to identify those that having high binding affinity to said substrate;
- and
- c. conjugating said identified aptamer or an otherwise available aptamer to pRNA trifurcate or four way X-motif junction domain, wherein said available aptamer mimics at least one antibody to said at least one substrate.
Dependencies are inferred from the claim text.