Vectors encoding HCN channels and MiRP1

• US 6,783,979 B2
• Filed: 06/06/2001
• Issued: 08/31/2004
• Est. Priority Date: 06/06/2001
• Status: Active Grant

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University), The Research Foundation for The State University of New York (State University of New York)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Cohen, Ira S., Rosen, Michael R., Robinson, Richard B., Yu, Han-Gang
• Primary Examiner(s): Marvich, Maria
• Application Number:
  US09/875,392
• Publication Number:
  US 20020188212A1
• Time in Patent Office: 1,182 Days
• Field of Search: 424/93.2, 435/320.1, 435/69.1, 435/91.1, 435/91.42, 435/235.1, 435/91.41, 435/456, 435/325, 514/44
• US Class Current: 435/320.1
• CPC Class Codes: A61K 38/1709 from mammals
• 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: G01N 33/5008 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• CPC Class Codes: G01N 33/502 for testing non-proliferative effects
• CPC Class Codes: G01N 33/5061 Muscle cells
• CPC Class Codes: G01N 33/6872 Intracellular protein regulatory factors and their receptors, e.g. including ion channels

Abstract

This invention provides for a chamber and system designed for use in assaying drug effects on heart rate. The chamber consists of a series of wells, each 3 mm by 3 mm in inner diameter. Cardiac myocytes disaggregated from neonatal animals are plated onto the bottom of each well and grown under standard tissue culture conditions. The chamber holds from 24-96 such wells. When drugs are to be assayed, the cells in each well are loaded with a calcium sensitive dye and the beating rate in each is monitored with a photodiode. Drug is added in graded concentrations to each well, and equilibrated and effects on rate are observed. This construct permits use of a cell based bioassay for the study of drugs or agents that may alter cardiac rate. This invention can be used in high throughput screening of drugs to evaluate/predict their effects on cardiac rate and rhythm. Further provided for by this invention is a vector which comprises a compound which encodes an ion channel.

Claims

1. A vector which comprises a nucleic acid molecule which encodes a HCN channel and a nucleic acid molecule which encodes a MiRP1.

2. The viral vector of claim 1, wherein the vector is a viral vector.

3. The viral vector of claim 2, which is an adenovirus.

4. The vector of claim 1, 3, wherein the vector is a plasmid or a cosmid.

5. The vector of claim 1, wherein the HCN channel is HCN1.

6. The vector of claim 1, 5, wherein the HCN channel is HCN2.

7. The vector of claim 1, wherein the HCN channel is HCN4.