# US 8,088,912 B2 · pRNA chimera

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- Number: US 8,088,912 B2
- Document ID: US8088912B2
- Status: Granted
- Kind: B2
- Application number: 10/539,241
- Filed: 2003-12-16
- Published: 2008-03-13
- Granted: 2012-01-03
- Earliest claimed: 2000-08-23
- Assignees: Purdue Research Foundation
- Inventors: Peixuan Guo; Stephen M. Hoeprich; Dan Shu
- Web page: https://patentgrep.com/patent/US8088912B2

## CPC

- C12N 15/111: {General methods applicable to biologically active non-coding nucleic acids}
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 35/00: Antineoplastic agents
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- C12N 15/1131: {against viruses}
- C12N 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- C12Y 113/11031: Arachidonate 12-lipoxygenase (1.13.11.31), i.e. lipoxygenase-type-12
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C12N 2310/11: Antisense
- C12N 2310/111: spanning the whole gene, or a large part of it
- C12N 2310/121: Hammerhead
- C12N 2310/16: Aptamers
- C12N 2310/3519: Fusion with another nucleic acid
- C12N 2310/53: partially self-complementary or closed
- C12N 2320/32: Special delivery means, e.g. tissue-specific
- C12N 2799/022: where the vector is derived from an adenovirus
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12Y: ENZYMES
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

A polyvalent multimeric complex formed from a plurality of circularly permuted chimeric pRNA molecules, each carrying a stabilized biologically active moiety.

## Claims

### Claim 1

A polyvalent multimeric complex comprising a plurality of chimeric pRNA monomers, each said chimeric pRNA monomer independently comprising a heterologous component that comprises a biologically active RNA.

### Claim 2 (depends on 1)

The polyvalent multimeric complex of claim 1 wherein the biologically active RNA is selected from the group consisting of a ribozyme, a siRNA, an RNA aptamer, an antisense RNA and a peptide nucleic acid (PNA).

### Claim 3 (depends on 1)

The polyvalent multimeric complex of claim 1 wherein the heterologous component of at least one chimeric pRNA monomer comprises an end-labeling agent.

### Claim 4 (depends on 3)

The polyvalent multimeric complex of claim 3 wherein the end-labeling agent is selected from the group consisting of biotin, pCp, DIG, SH group and phosphate.

### Claim 5 (depends on 1)

The polyvalent multimeric complex of claim 1 wherein at least one of the chimeric pRNA monomers is a circularly permuted pRNA.

### Claim 6 (depends on 1)

The polyvalent multimeric complex of claim 1 wherein at least one of the chimeric pRNA monomers incorporates at least one nucleotide analog or modified nucleotide.

### Claim 7 (depends on 6)

The polyvalent multimeric complex of claim 6, wherein the nucleotide analog or modified nucleotide is selected from the group consisting of a 2′-F-2′ deoxy nucleotide derivative, a phosphorothoiate, a 2′-O-methyl ribonucleotide, a peptide nucleic acid (PNA).

### Claim 8 (depends on 1)

A method for delivering a therapeutic agent to a cell comprising:
contacting the cell with the polyvalent multimeric complex of claim 1, wherein the heterologous component of a first chimeric pRNA monomer comprises a first biologically active RNA and the heterologous component of a second chimeric pRNA monomer comprises a second biologically active RNA that is an RNA aptamer which specifically binds a cell membrane component, such that the polyvalent multimeric complex is taken up by the cell.

### Claim 9 (depends on 8)

The method of claim 8 wherein the cell membrane component to which the polyvalent multimeric complex binds is a receptor, and wherein the polyvalent multimeric complex is taken up by the cell via receptor-mediated endocytosis.

### Claim 10

A chimeric pRNA monomer comprising 5′ and 3′ ends, wherein at least one of said 5′ and 3′ ends comprises a heterologous component that comprises a biologically active RNA, and wherein the chimeric pRNA monomer is capable of assembling into a polyvalent multimeric complex comprising a plurality of chimeric pRNA monomers.

### Claim 11 (depends on 10)

The pRNA monomer of claim 10 wherein the heterologous component comprises antisense RNA.

### Claim 12 (depends on 10)

The pRNA monomer of claim 10 wherein the heterologous component comprises an aptamer.

### Claim 13 (depends on 10)

The pRNA monomer of claim 10 wherein the heterologous component comprises a labeling agent.

### Claim 14 (depends on 13)

The pRNA monomer of claim 13 wherein the labeling agent is selected from the group consisting of biotin, pCp, DIG, SH group and phosphate.

### Claim 15 (depends on 14)

The pRNA monomer of claim 14 comprising at least one nucleotide analog or modified nucleotide.

### Claim 16 (depends on 15)

The pRNA monomer of claim 15, wherein the nucleotide analog or modified nucleotide is selected from the group consisting of a 2′-F-2′ deoxy nucleotide derivative, a phosphorothioate, a 2′-O-methyl ribonucleotide, a peptide nucleic acid (PNA).

### Claim 17 (depends on 10)

The chimeric pRNA monomer of claim 10 comprising at least one nucleotide analog or modified nucleotide.

### Claim 18 (depends on 17)

The chimeric pRNA monomer of claim 17 which is a circularly permuted pRNA.

### Claim 19 (depends on 17)

The chimeric pRNA monomer of claim 17 wherein the nucleotide analog or modified nucleotide is selected from the group consisting of a 2′-F-2′ deoxy nucleotide derivative, a phosphorothioate, a 2′-O-methyl ribonucleotide, a peptide nucleic acid (PNA).