Inventors:
Paul Anderson - Belmont MA, US
Pavel Ivanov - Brighton MA, US
Mohammed Emara - Newton MA, US
Assignee:
THE BRIGHAM AND WOMEN'S HOSPITAL, INC. - Boston MA
International Classification:
C07H 21/02
US Classification:
514 44 R, 536 245, 435375
Abstract:
Provided herein are neuroprotective molecules containing a sequence of 25-35 contiguous nucleotides that is at least 80% identical to a contiguous sequence between nucleotide 1 and nucleotide 50 of a mature human tRNA and at least four contiguous guanosine-containing nucleotides, where the sequence of 25-35 contiguous nucleotides contains a D-loop stem structure, the at least four contiguous guanosine-containing nucleotides are located at the 5′ end of the neuroprotective molecule, and the neuroprotective molecule contains at least one deoxyribonucleotide. Also provided are molecules containing a sequence of 25-35 contiguous nucleotides that is at least 80% identical to a contiguous sequence between nucleotide 1 and nucleotide 50 of a mature human tRNA selected from the group of tRA, tRNA, tRNA, tRNA, tRNA, tRNA, tRN, tRNA, tRNA, tRNA, tRNA, tRNA, tRNA, tRNA, tRNA, tRNA, tRNA, tRNA, tRNA, and tRNA; and at least four contiguous guanosine-containing nucleotides, where the sequence of 25-35 contiguous nucleotides contains a D-loop stem structure and the at least four contiguous guanosine-containing nucleotides are located at the 5′ end of the neuroprotective molecule. Also provided are methods of inducing or increasing stress granule formation in a cell, decreasing protein translation in a cell, decrease stress-induced cell death, or treating a neurological disorder associated with neuron death in a subject using at least one of these neuroprotective molecules or a C-myeoligonucleotide. Also provided are methods of identifying a candidate translation inhibitory nucleic acid.