Intracerebral Infusion of Antisense Oligonucleotides Into Prion-infected Mice.
Mice deficient for the cellular prion protein (PrP(C)) do not develop prion disease; accordingly, gene-based strategies to diminish PrP(C) expression are of interest. We synthesized a series of chemically modified antisense oligonucleotides (ASOs) targeted against mouse Prnp messenger RNA (mRNA) and identified those that were most effective in decreasing PrP(C) expression. Those ASOs were also evaluated in scrapie-infected cultured cells (ScN2a) for their efficacy in diminishing the levels of the disease-causing prion protein (PrP(Sc)). When the optimal ASO was infused intracerebrally into FVB mice over a 14-day period beginning 1 day after infection with the Rocky Mountain Laboratory (RML) strain of mouse prions, a prolongation of the incubation period of almost 2 months was observed. Whether ASOs can be used to develop an effective therapy for patients dying of Creutzfeldt-Jakob disease remains to be established.
Institute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, California, USA.
Karah
K
Nazor Friberg
Gene
G
Hung
Ed
E
Wancewicz
Kurt
K
Giles
Chris
C
Black
Sue
S
Freier
Frank
F
Bennett
Stephen J
SJ
Dearmond
Yevgeniy
Y
Freyman
Pierre
P
Lessard
Sina
S
Ghaemmaghami
Stanley B
SB
Prusiner