Antisense oligonucleotides (ASO), short single-stranded polymers based on DNA or RNA chemistries and synthesized in vitro, regulate gene expression by binding in a sequence-specific manner to an RNA target. The functional activity and selectivity in the action of ASOs largely depends on the combination of nitrogenous bases in a target sequence. This simple and natural property of nucleic acids provides an attractive route by which scientists can create different ASO-based techniques. Over the last 50 years, planned and realized applications in the field of antisense and nucleic acid nanotechnologies have produced astonishing results and posed new challenges for further developments, exemplifying the essence of the post-genomic era. Today the majority of ASOs are chemically modified and/or incorporated within nanoparticles to enhance their stability and cellular uptake. This review critically analyzes some successful cases using the antisense approach in medicine to address severe diseases, such as Duchenne muscular dystrophy and spinal muscular atrophy, and suggests some prospective directions for future research. We also examine in detail the elaboration of unmodified insect-specific DNA insecticides and RNA preparations in the areas of agriculture and forestry, a relatively new branch of ASO that allows circumvention of the use of non-selective chemical insecticides. When considering the variety of successful ASO modifications with an efficient signal-to-noise ratio of action, coupled with the affordability of in vitro oligonucleotide synthesis and post-synthesis procedures, we predict that the next half-century will produce a fruitful yield of tools created from effective ASO-based end products.
Abstract. We construct and prove asymptotic expansions at infinity for solutions of Neumann problems and matching problems for systems of second order differential equations in regions with corner outlets to infinity. Outside some disc the regions are either periodic or deformed by parabolic inclusions. In addition to logarithmicpolynomial solutions, the asymptotic expansions contain components of the type of boundary layer that either exponentially decay away from the boundary or are localized inside the parabolic inclusions. Operators of the problems become Fredholm operators, and remainders in asymptotic expansions are estimated in scales of function spaces with norms determined by double weight factors and their step distribution. We consider also other types of problems which allow us to apply the developed methods for reduction to a model problem in a sector and for recovery of properties of remainders near perturbed boundary; in particular, we consider the matching problem in regions with irregular points of peak-like inclusion type.1. Statement of the problem and preliminary description of results 1.1. Regions. Let K = {x : r > 0, ϕ ∈ (−α, α)} be a sector in the plane R 2 with vertex at O, where x = (x 1 , x 2 ) and (r, ϕ) are Cartesian and polar coordinates so that x 1 = r cos ϕ, x 2 = r sin ϕ, and α ∈ (0, π] is the half-angle of the sector. We also introduce Cartesian coordinates y ± = (y ± 1 , y ± 2 ) with the axes y ± 1 directed along the sides (∂K) ± = {x : r > 0, ϕ = ±α} of the sector, and the axes y
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