DENDRITIC NUCLEIC-ACID STRUCTURES

Dendritic molecules are highly-branched arborescent structures and hav e found applications as chemical reagents, lubricants, contrast media for magnetic resonance, and others. Dendritic nucleic acids could be e xtremely useful for the development of nucleic acid diagnostics as sig nal amplification tools and potentially as drug (antisense) delivery v ehicles. Further, due to the relatively large size of nucleic acid mol ecules, nucleic acid dendrimers could be readily labeled with numerous fluorescent compounds and/or protein moieties with limited steric hin drance and/or quenching. Herein, we present a physical-mathematical mo del of a new class of dendrimers, constructed entirely from unique nuc leic acid monomers that are designed such that sequential hybridizatio n adds successive layers of monomer in a geometric expansion of both m ass and free single-stranded sequences, called arms, at the surface. T he specially designed monomer is a heterodimer of two single-stranded nucleic acid oligomers possessing a central double-stranded waist and four single-stranded arms for binding. Assembly of a dendrimer is init iated from a single monomer and proceeds in layers, the first layer co mprising four monomers, which provides 12 single-stranded arms. Thus, the second layer adds 12 monomers resulting in 36 singled-stranded arm s. After addition of the 6th layer, the dendrimer is comprised of 1457 monomers, of which 972 reside in the 6th layer, which possesses 2916 single-stranded arms. The accompanying mathematical description of a d endrimer's growth is generic. A natural consequence and limiting condi tion of the growth process we describe is a saturated solution of nucl eic acid, which is, in effect, a ''nucleic acid membrane''. (C) 1997 A cademic Press Limited.