US 7,538,202 B2
Enzyme-free isothermal exponential amplification of nucleic acids and nucleic acid analog signals
David Zhang, Overland Park, Kans. (US); Bernard Yurke, Plainfield, N.J. (US); and Erik Winfree, Altadena, Calif. (US)
Assigned to California Institute of Technology, Pasadena, Calif. (US)
Filed on Dec. 09, 2004, as Appl. No. 11/9,386.
Claims priority of provisional application 60/531519, filed on Dec. 19, 2003.
Prior Publication US 2005/0227259 A1, Oct. 13, 2005
Int. Cl. C07H 21/04 (2006.01); C12Q 1/68 (2006.01)
U.S. Cl. 536—23.1  [435/6] 21 Claims
 
1. An amplifier nucleic acid molecule 1, comprising:
a) a first damping oligonucleotide 10, which comprises, in operative linkage in a 5′ to 3′ orientation,
a first toehold domain 210 comprising at least two nucleotides, and
at least two first propagating oligonucleotide binding domains 230 and 240, each of binding domains 230 and 240 comprising at least six nucleotides; and
b) at least one first propagating oligonucleotide 40, which comprises, in operative linkage in a 3′ to 5′ orientation,
a first domain 130, which is complementary to and selectively hybridizes the first propagating oligonucleotide binding domain 230,
at least two sets of individual domains 150 and 160 arranged in alternating order, wherein each of domains 150 and 160 are not complementary to the first damping oligonucleotide 10, and wherein each domain 150 has an identical nucleic acid sequence and each domain 160 has an identical nucleic acid sequence, and wherein each of domains 150 and 160 have different nucleic acid sequences, and wherein each of domains 150 and 160 comprises at least six nucleotides, and
a sixth domain 140, which is complementary to and selectively hybridizes to the first propagating oligonucleotide binding domain 240,
wherein the amplifier nucleic acid molecule 1 comprises a complex comprising the first damping oligonucleotide 10 and the first propagating oligonucleotide 40, and wherein the nucleic acid molecule 1, the first damping oligonucleotide 10, and the first propagating oligonucleotide 40 do not comprise domains which are complementary or selectively hybridize to a target sequence to be identified by the complex.