Systematic evolution of ligands by exponential enrichment: tissue SELEX

• US 6,376,474 B1
• Filed: 09/14/1999
• Issued: 04/23/2002
• Est. Priority Date: 05/03/1995
• Status: Expired due to Fees

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Sciences Inc.
• Inventors: Gold, Larry, Heilig, Joseph S.
• Primary Examiner(s): Zitomer, Stephanie W.
• Application Number:
  US09/396,002
• Time in Patent Office: 952 Days
• Field of Search: 514/44, 424/1.73, 424/9.1, 424/450, 530/350, 536/23.1, 435/6
• US Class Current: 514/44.00R
• CPC Class Codes: 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
• CPC Class Codes: A61K 47/547 Chelates, e.g. Gd-DOTA or Zinc-amino acid chelates; Chelate-forming compounds, e.g. DOTA or ethylenediamine being covalently linked or complexed to the pharmacologically- or therapeutically-active agent
• CPC Class Codes: A61K 47/549 Sugars, nucleosides, nucleotides or nucleic acids
• CPC Class Codes: C12N 15/1048 SELEX
• 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 2310/18 acting by a non-sequence specific mechanism other than C12N2310/16 or C12N2310/17
• CPC Class Codes: C12Q 1/6811 Selection methods for production or design of target specific oligonucleotides or binding molecules

Abstract

This invention discloses high-affinity oligonucleotide ligands to complex tissue targets, specifically nucleic acid ligands having the ability to bind to complex tissue targets, and the methods for obtaining such ligands. Tissue targets comprise cells, subcellular components, aggregates or cells, collections of cells, and higher ordered structures. Specifically, nucleic acid ligands to red blood cells ghosts, endothelia of the blood brain and CSF-blood barriers, glioblastomas, and lymphomas are described.

Claims

1. A method of delivering a pharmaceutical to the brain comprising:

conjugating the pharmaceutical to a nucleic acid ligand of a transporter molecule that is specific to or enhanced in a tissue which acts as a barrier to the brain, to form a ligand-pharmaceutical conjugate; and

administering the ligand-pharmaceutical conjugate to an animal in need of the pharmaceutical, whereby a transporter molecule-ligand-pharmaceutical conjugate complex is formed and whereby the pharmaceutical is delivered to the brain.

2. The method of claim 1 wherein said tissue is cerebral endothelium.

3. The method of claim 1 wherein said tissue is choroid plexus epithelium.