Aptamer-mRNA conjugates for targeted protein or peptide expression and methods for their use

• US 8,916,696 B2
• Filed: 06/12/2012
• Issued: 12/23/2014
• Est. Priority Date: 06/12/2011
• Status: Active Grant

• Current Assignee: City of Hope
• Original Assignee: City of Hope
• Inventors: Rossi, John J., Bobbin, Maggie
• Primary Examiner(s): Chong, Kimberly
• Application Number:
  US13/494,880
• Publication Number:
  US 20130022538A1
• Time in Patent Office: 924 Days
• Field of Search: None
• US Class Current: 536/24.5
• CPC Class Codes: A61K 38/465 acting on ester bonds (3.1), e.g. lipases, ribonucleases
• CPC Class Codes: A61K 47/549 Sugars, nucleosides, nucleotides or nucleic acids
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 49/0054 Macromolecular compounds, i.e. oligomers, polymers, dendrimers
• CPC Class Codes: A61K 49/12 Macromolecular compounds
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 15/111 General methods applicable to biologically active non-coding nucleic acids
• CPC Class Codes: C12N 15/1132 against retroviridae, e.g. HIV
• CPC Class Codes: C12N 15/115 Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2310/16 Aptamers
• CPC Class Codes: C12N 2310/3519 Fusion with another nucleic acid
• CPC Class Codes: C12N 2320/32 : Special delivery means, e.g. tissue-specific
• CPC Class Codes: C12Y 301/21004 : Type II site-specific deoxyribonuclease (3.1.21.4)

Abstract

An aptamer-mRNA conjugate is provided. The aptamer-mRNA conjugate may include an aptamer component that binds a membrane associated protein on a target cell and an mRNA component that is expressed by the target cell.

Claims

1. An aptamer-mRNA conjugate comprising:

an aptamer component that binds a membrane associated protein on a target cell; and

an mRNA component that is expressed by the target cell, wherein the mRNA component is an mRNA molecule.

2. The aptamer-mRNA conjugate of claim 1, wherein the membrane associated protein is CD4, CD19, DC-SIGN/CD209, HIV envelope glycoprotein gp120, CCR5, EGFR/ErbB1, EGFR2/ErbB2/HER2, EGFR3/ErbB3, EGFR4/ErbB4, EGFRvIII, Transferrin Receptor, PSMA, VEGF, VEGF-2, CD25, CD11a, CD33, CD20, CD3, CD52, CEA, TAG-72, LDL receptor, insulin receptor, megalin receptor, LRP, mannose receptor, P63/CKAP4 receptor, arrestin, ASGP, CCK-B, HGFR, RON receptor, FGFR, ILR, AFP, CA125/MUC16, PDGFR, stem cell factor receptor, colony stimulating factor-1 receptor, integrins, TLR, BCR or BAFF-R.

3. The aptamer-mRNA conjugate of claim 1, wherein the mRNA component is a therapeutic agent.

4. The mRNA component of claim 3, wherein the therapeutic agent is a cytotoxin, an enzyme, or an antibody or functional fragment thereof.

5. The aptamer-mRNA conjugate of claim 1, wherein the mRNA component is a fluorescent or bioluminescent protein.

6. An aptamer-mRNA conjugate comprising:

an aptamer component that binds a membrane associated protein on a target cell, wherein the aptamer component comprises SEQ ID NO;

1 or SEQ ID NO;

2, and

an mRNA component that is expressed by the target cell.

7. The aptamer-mRNA conjugate of claim 6, wherein the mRNA component is a fluorescent or bioluminescent protein.