Property effecting and/or property exhibiting compositions for therapeutic and diagnostic uses

• US 8,735,145 B2
• Filed: 10/30/2007
• Issued: 05/27/2014
• Est. Priority Date: 12/15/1995
• Status: Expired due to Term

• Current Assignee: Enzo Biochem Incorporated
• Original Assignee: Enzo Biochem Incorporated
• Inventors: Rabbani, Elazar, Stavrianopoulos, Jannis G., Donegan, James J., Liu, Dakai, Engelhardt, Dean L., Keller, Norman E.
• Primary Examiner(s): Chong, Kimberly
• Application Number:
  US11/929,897
• Publication Number:
  US 20080248564A1
• Time in Patent Office: 2,401 Days
• US Class Current: 435/320.1
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 14/62 Insulins
• CPC Class Codes: C12N 15/1132 against retroviridae, e.g. HIV
• CPC Class Codes: C12N 15/87 Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
• CPC Class Codes: C12N 2740/16322 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 9/1247 DNA-directed RNA polymerase (2.7.7.6)
• CPC Class Codes: C12Q 1/6897 involving reporter genes operably linked to promoters
• CPC Class Codes: C12Q 1/703 Viruses associated with AIDS
• CPC Class Codes: C12Q 2525/301 Hairpin oligonucleotides
• CPC Class Codes: C12Q 2525/307 Circular oligonucleotides

Abstract

The present invention provides an array of compositions useful for effecting and/or exhibiting changes in biological functioning and processing within cells and in biological systems containing such cells. In effect, these compositions combine chemical modifications and/or ligand additions with biological functions. The chemical modifications and/or ligand additions provide additional characteristics to the compositions without interfering substantially with their biological function. Such additional characteristics include nuclease resistance, targeting specific cells or specific cell receptors localizing to specific sites within cells and augmenting interactions between the compositions and target cells of interest as well as decreasing such interactions when desired. Also provided by the present invention are processes and kits.

Claims

1. A chemically modified double-stranded nucleic acid construct, wherein solely one strand of said construct comprises a modified nucleotide, a nucleotide analog, or a combination of the foregoing, wherein said modified nucleotide or nucleotide analog is covalently attached to a non-nucleic acid entity, wherein said non-nucleic acid entity is a polymer, wherein the unmodified strand of said construct when present in a cell is used as a template for the synthesis of a nucleic acid product having biological activity, and wherein said polymer is covalently attached to said modified nucleotide on the base moiety.

2. The chemically modified double-stranded nucleic acid construct of claim 1, wherein said nucleic acid product is selected from the group consisting of antisense RNA, antisense DNA, sense RNA, ribozymes, messenger RNA, and a combination of any of the foregoing.

3. The chemically modified double-stranded nucleic acid construct of claim 1, wherein said non-nucleic acid entity confers nuclease resistance, cell targeting, cellular localization or nuclear localization, or a combination of the foregoing.

10. The chemically modified double-stranded nucleic acid construct of claim 1, wherein said non-nucleic acid entity confers nuclease resistance, cell targeting, cellular localization or nuclear localization, or a combination of the foregoing.

4. A chemically modified double-stranded nucleic acid construct, wherein solely one strand of said construct comprises a modified nucleotide, a nucleotide analog, or a combination of the foregoing, wherein said modified nucleotide or nucleotide analog is covalently attached to a non-nucleic acid entity that is a polymer, wherein the unmodified strand of said construct when present in a cell is used as a template for the synthesis of a nucleic acid product having biological activity, and wherein said polymer is selected from a polycation, a matrix protein, a lectin, or a protein that functions in integration of nucleic acid into DNA.

5. The chemically modified double-stranded nucleic acid construct of claim 4, wherein said polymer is attached to said modified nucleotide on the base moiety.

6. The chemically modified double-stranded nucleic acid construct of claim 4, wherein said polymer is attached to said modified nucleotide on the sugar moiety.

7. The chemically modified double-stranded nucleic acid construct of claim 4, wherein said polymer is attached to said modified nucleotide on the phosphate moiety.

8. A chemically modified double-stranded nucleic acid construct, wherein solely one strand of said construct comprises a modified nucleotide, a nucleotide analog, or a combination of the foregoing, wherein said modified nucleotide or nucleotide analog is covalently attached to a non-nucleic acid entity, wherein said non-nucleic acid entity is a polymer, wherein the unmodified strand of said construct when present in a cell is used as a template for the synthesis of a nucleic acid product having biological activity, and wherein said polymer is covalently attached to said modified nucleotide on the sugar moiety.

9. The chemically modified double-stranded nucleic acid construct of claim 8, wherein said nucleic acid product is selected from the group consisting of antisense RNA, antisense DNA, sense RNA, ribozymes, messenger RNA, and a combination of any of the foregoing.

11. A chemically modified double-stranded nucleic acid construct wherein a first strand of said construct comprises more than one modified nucleotide, nucleotide analog, or combination thereof, wherein a second strand of said construct lacks said modified nucleotide, nucleotide analog or combination thereof, wherein said second strand is hybridized to said first strand and wherein said modified nucleotide or nucleotide analog is covalently attached to a non-nucleic acid entity, wherein said non-nucleic acid entity is a polymer, wherein the unmodified strand of said construct when present in a cell is used as a template for the synthesis of a nucleic acid product having biological activity.

12. The chemically modified double-stranded nucleic acid construct of claim 11, wherein said polymer is attached to said more than one modified nucleotide on the base moiety.

13. The chemically modified double-stranded nucleic acid construct of claim 11, wherein said polymer is attached to said more than one modified nucleotide on the sugar moiety.