Biological macromolecules, including DNA, RNA, and proteins, have intrinsic features that make them potential building blocks for the bottom-up fabrication of nanodevices. DNA nanotechnology is a subfield of nanotechnology that seeks to use the unique molecular-recognition properties of DNA and other nucleic acids to create novel, controllable structures of DNA. Chemically, DNA consists of two long polymers. DNA is normally a linear molecule, in that its axis is unbranched. Different results are obtained when DNA in aqueous solution and DNA in biological tissue are exposed to ultrasound. The influence of ultrasonic waves on native DNA molecules has been previously reported.[1] In those studies, it was shown that 2 min of ultrasonication of an aqueous solution of DNA splits the DNA helix into fragments; this makes ultrasonication a useful and convenient tool for obtaining DNA fragments on a preparative scale. Here, we show, for the first time, that ultrasonic waves can be used to convert native DNA molecules to extremely stable DNA nanoparticles (DNA nanospheres, DNs). In addition, the genetic information that was encoded in the DNA nanospheres was successfully delivered to competent cells and to human U2OS cancer cells, and expressed in competent (E. coli) cells. Our fundamental research on the synthesis and characterization of sonochemically produced DNA nanospheres provides an estimate of the efficiency of the sonochemical process in converting the native DNA molecules to biologically active DNA nanospheres.Ultrasonic emulsification is a well-known process that occurs in biphasic systems. [2][3] Emulsification is necessary for microcapsule formation. Micrometer-sized gas-or liquid-filled micro/ nanospheres can be produced from various kinds of proteins such as bovine serum albumin (BSA), [4][5][6] human serum albumin (HSA), [7] hemoglobin (Hb), [8] and from combination of proteins.[9] The mechanism of the sonochemical formation of protein microspheres (PMs) has been discussed previously.[10] The microspheres are formed by chemically crosslinking cysteine residues, which undergo oxidation by HO 2 radicals formed around a micron-sized gas bubble or a nonaqueous droplet. The formation of SÀS bonds is a direct result of the chemical effects of the ultrasound radiation on an aqueous medium.Our reaction involved the sonication of an aqueous solution of DNA and dodecane (or soya oil) in a 50 mL sonication cell for three minutes. Five kinds of DNA were used in this work: 1) genomic DNA extracted from cells, 2) genomic DNA extracted from leaves, 3) DNA plasmid, 4) linear DNA extracted from DNA plasmid, and 5) single-stranded DNA. For all five DNAs and for both organic solvents we obtained DNA nanospheres. No difference was found between DNA nanospheres filled with dodecane and those filled with soya oil. We further demonstrate that the denaturing conditions as well as denaturing agents, which are commonly used in DNA isolation, cannot destroy the dsDNA (double-stranded DNA) nanospheres of the four DNA's, while the nanos...