A newer design strategy (Yamazoe et al., 2012, Angew. In this example, MO-mRNA hybridization was sterically blocked until the caging groups were released from the nucleobases (Dieters et al., 2010, J. subsequently presented caged MOs where multiple caged nucleotide monomers were incorporated during solid-phase synthesis (Dieters et al., 2010, J. 3:650-651 Tomasini et al., 2009, Genesis 47:736-743) employed a complementary sense strand and photocleavable linker. Initial caged antisense oligos (Tang and Dmochowski, 2006, Angew. Synthetic challenges of site-specifically incorporating one or more photolabile moieties within a large oligonucleotide, and limitations arising from the available near-UV-activatible caging moieties, have slowed such development.Ī particular focus for caged oligo development has been antisense morpholinos (MOs), which are commonly used to block mRNA translation and modify pre-mRNA splicing in a variety of model organisms, including mouse, zebrafish, frog, sea urchin, and chick (Eisen and Smith, 2008, Development 135:1735-1743). Less investigated are caged oligonucleotides, despite the central roles played by DNA and RNA in biology, and the tantalizing potential for being able to turn genes “on” or “off” with light. In each case, photoactivation with high spatiotemporal control can be achieved using a focused laser beam of suitable wavelength. 5:999-1005), whose latent biological activity can be revealed with light, have been widely adopted, particularly for the study of amino acids (Saliemo et al., 2008, Eur. More generally, “caged” molecules (Young and Dieters, 2007, Org. For example, channelrhodopsin-a single component, light-activated cation channel protein from algae-was co-opted in the development of pioneering optogenetic approaches for manipulating the activity of specific neurons and controlling animal behavior (Boyden et al., 2005, Nat. Photochemical methods for regulating the structure, function, and/or localization of molecular species enable the manipulation of advanced materials (e.g., silicon computer chips) as well as complex biological systems. The government has certain rights in the invention. This invention was made with government support under RO1 GM083030 awarded by the National Institute of Health. STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 9, 2014, the disclosures of which are incorporated herein by reference in their entirety. 4, 2015, which is entitled to priority under 35 U.S.C. § 371 claiming benefit to International Patent Application No. national phase application filed under 35 U.S.C.
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