Functionalized nucleic acid nanostructures for RNA delivery
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Publication Number
US-11305019-B2
Publication Date
2022-04-19
Expiration Date
Abstract
The present disclosure provides cell-penetrating nucleic acid nanostructures well suited as transfection reagents for the delivery of bioactive agents to cells both in vivo and in vitro for research, diagnostic, and/or therapeutic purposes.
Core Innovation
The invention relates to a nucleic acid nanostructure that includes a DNA or RNA scaffold with at least one single stranded nucleic acid staple strand complementary to the scaffold. At least one positively charged cell penetrating peptide is attached to the at least one staple strand, and at least one therapeutic substance is also attached to the at least one staple strand. The nanostructure further includes non-conjugated overhangs and cell penetrating peptide-conjugated overhangs.
The therapeutic substance is selected from siRNA, miRNA, shRNA, asRNA, mRNA, crRNA, tracrRNA, and a RNA vaccine. In the disclosed examples, functionalized 24 helix bundle DNA origami nanostructures are decorated with cell-penetrating peptides and siRNA duplexes, with overhang-based attachment using non-conjugated and cell penetrating peptide-conjugated overhangs.
The disclosed system is described as enabling cellular uptake and therapeutic effects in a manner associated with non-endocytic/direct penetration, attributed to the positively charged cell penetrating peptides. The document also addresses stability and use in challenging media conditions, and reports gene silencing activity in vitro.
Claims Coverage
The independent claims cover three main categories: a nucleic acid nanostructure with positively charged cell penetrating peptides and therapeutic substances attached to complementary staple strands, treatment methods administering that nanostructure to a subject, and structural features including non-conjugated overhangs and cell-penetrating-peptide-conjugated overhangs, with therapeutic substances selected from defined RNA therapeutics.
Nucleic acid nanostructure with positively charged cell penetrating peptide and therapeutic substance on staple strands
A nucleic acid nanostructure comprising a DNA or RNA scaffold, at least one single stranded nucleic acid staple strand complementary to the scaffold, at least one cell penetrating peptide attached to the at least one staple strand, and at least one therapeutic substance attached to the at least one staple strand, wherein the at least one cell penetrating peptide is positively charged.
Overhang architecture using non-conjugated overhangs and cell-penetrating-peptide-conjugated overhangs
A nucleic acid nanostructure wherein the nanostructure includes non-conjugated overhangs and cell penetrating peptide-conjugated overhangs.
Therapeutic agent selection for the nucleic acid nanostructure
A nucleic acid nanostructure wherein the at least one therapeutic agent is selected from siRNA, miRNA, shRNA, asRNA, mRNA, crRNA, tracrRNA, and a RNA vaccine.
Treatment method by administering the structured nucleic acid nanostructure
A method of treating a subject comprising providing a nucleic acid nanostructure having a DNA or RNA scaffold, at least one single-stranded nucleic acid staple strand complementary to the scaffold, at least one positively charged cell penetrating peptide attached to the at least one staple strand, and at least one therapeutic substance attached to the at least one staple strand; wherein the nanostructure includes non-conjugated overhangs and cell penetrating peptide-conjugated overhangs; wherein the at least one therapeutic agent is selected from siRNA, miRNA, shRNA, asRNA, mRNA, crRNA, tracrRNA, and a RNA vaccine; and administering a therapeutically effective amount of the nucleic acid nanostructure to a subject.
Across the independent claims, the core inventive coverage is a nucleic acid nanostructure with a DNA or RNA scaffold and complementary staple strands, where positively charged cell penetrating peptides and therapeutic substances are attached to the staple strands, and where the nanostructure includes both non-conjugated overhangs and cell-penetrating-peptide-conjugated overhangs. The treatment independent claims cover administering a therapeutically effective amount of that nanostructure to a subject.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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