Nucleic acid mediated electron transfer

• US 6,277,576 B1
• Filed: 05/07/1999
• Issued: 08/21/2001
• Est. Priority Date: 12/10/1993
• Status: Expired due to Term

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Kayyem, Jon Faiz, Meade, Thomas J., Fraser, Scott E.
• Primary Examiner(s): ZITOMER, STEPHANIE W
• Application Number:
  US09/306,768
• Time in Patent Office: 837 Days
• Field of Search: 435/6, 536/23.1, 536/24.3
• US Class Current: 435/6.11
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C07H 23/00 Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12 esters with inorganic acids C07H11/00; metal salts, see parent compounds
• CPC Class Codes: C12Q 1/6818 involving interaction of two or more labels, e.g. resonant energy transfer
• CPC Class Codes: C12Q 1/6825 Nucleic acid detection involving sensors
• CPC Class Codes: C12Q 2563/113 the label being electroactive, e.g. redox labels
• CPC Class Codes: C12Q 2563/137 Metal/ion, e.g. metal label
• CPC Class Codes: C12Q 2565/101 Interaction between at least two labels
• CPC Class Codes: C12Q 2565/1015 labels being on the same oligonucleotide
• CPC Class Codes: C12Q 2565/401 Signal amplification by chemical polymerisation
• CPC Class Codes: C12Q 2565/607 being a sensor, e.g. electrode
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention provides for the selective covalent modification of nucleic acids with redox active moieties such as transition metal complexes. Electron donor and electron acceptor moieties are covalently bound to the ribose-phosphate backbone of a nucleic acid at predetermined positions. The resulting complexes represent a series of new derivatives that are bimolecular templates capable of transferring electrons over very large distances at extremely fast rates. These complexes possess unique structural features which enable the use of an entirely new class of bioconductors and photoactive probes.

Claims

1. A method for detecting the presence of a target sequence in a nucleic acid sample comprising:

a) applying an AC input signal to a hybridization complex, wherein said hybridization complex comprises;

i) a first single stranded nucleic acid comprising an electrode; and

ii) a target sequence containing at least one moiety capable of donating or accepting an electron; and

b) detecting electron transfer between said moiety capable of donating or accepting an electron and said electrode.

3. A method according to claim 1 or 2 wherein said AC input signal is applied at a plurality of frequencies.

4. A method according to claim 1 or 2 wherein said detecting is done by receiving an output signal characteristic of electron transfer between said moiety and said electrode.

5. A method according to claim 4 wherein said output signal is a current.

2. A method for detecting the presence of a target sequence in a nucleic acid sample comprising:

a) applying an AC input signal to a hybridization complex, wherein said hybridization complex comprises;

i) an electron transfer mediator;

ii) a first single stranded nucleic acid comprising an electrode; and

iii) a target sequence containing at least one moiety capable of donating or accepting an electron; and

b) detecting electron transfer between said moiety capable of donating or accepting an electron and said electrode.