Oligonucleotides for the inhibition of human eg5 expression

Details Oligonucleotides for the inhibition of human eg5 expression Oligonucleotides for the inhibition of human eg5 expression

2000-07-27

2002-10-29

McGarry, Sean (Department: 1635)

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

C435S006120, C435S375000, C435S377000, C435S455000, C536S023100, C536S024100, C536S025300, C514S04400A

Reexamination Certificate

active

06472521

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to an oligonucleotide or a derivative thereof corresponding to a particular fragment of a nucleic acid sequence encoding a human eg5 or a mutant form thereof. The invention further relates to a method of making the oligonucleotide and the use thereof.
BACKGROUND OF THE INVENTION
During mitosis a microtubule-based spindle apparatus helps distribute the duplicated chromosomes equally to the daughter cells. Kinesin-related motor proteins are part of the forces required for spindle assembly and chromosome segregation. The formation of a bipolar mitotic spindle involves the activity of many different motor proteins. One human kinesin-related motor protein is human eg5, which interacts with the mitotic centrosomes and has been shown to be essential for bipolar spindle formation (Blangy et al., Cell (1995)83, 1159). Microinjection of specific anti-human-eg5 antibodies blocks centrosome migration and causes cells to arrest in mitosis.
Another method for blocking bipolar spindle formation is the inhibition of eg5 expression. One way to specifically inhibit eg5 expression is by the use of antisense oligonucleotides, which can be optionally modified in order to improve their properties (E. Uhlmann and A. Peyman,
Chemical Reviews
90:543 (1990); S. Agrawal,
TIBTECH
1996:376). Antisense oligonucleotides are thought to bind to specific sequences of the mRNA, resulting in degradation of the mRNA and/or inhibition of protein synthesis.
SUMMARY OF THE INVENTION
The present invention provides an oligonucleotide or a derivative thereof corresponding to a fragment of the nucleic acid sequence encoding an eg5 gene—preferably, human eg5 or a pathogenic organism's eg5, e.g.,
Plasmodium falciparum
(malaria). For example, the oligonucleotide comprises from 8 to about 100 nucleotides, preferably from about 8 to about 20 nucleotides of the eg5 sequence. The oligonucleotide or derivative thereof binds to the nucleic acid sequence of eg5 and inhibits the formation of the eg5 protein. The human eg5 nucleic acid sequence has been reported (Blangy et al.,
Cell
83:1159 (1995)). SEQ ID NO.: 20 is an example of a nucleic acid sequence that encodes human eg5. SEQ ID NO.: 21 is an example of a
Plasmodium falciparum
eg 5 nucleic acid sequence.


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