Promising nucleic acid analogs and mimics: characteristic features and applications of PNA, LNA, and morpholino

Abstract

Nucleic acid analogs and mimics are commonly the modifications of native nucleic acids at the nucleobase, the sugar ring, or the phosphodiester backbone. Many forms of promising nucleic acid analogs and mimics are available, such as locked nucleic acids (LNAs), peptide nucleic acids (PNAs), and morpholinos. LNAs, PNAs, and morpholinos can form both duplexes and triplexes and have improved biostability. They have become a general and versatile tool for DNA and RNA recognition. LNA is a general and versatile tool for specific, high-affinity recognition of single-stranded DNA (ssDNA) and single-stranded RNA (ssRNA). LNA can be used for designing LNA oligoes for hybridization studies or as real time polymerase chain reaction probes in the form of Taqman probes. LNA also has therapeutic and diagnostic applications. PNA is another type of DNA analog with neutral charge. The extreme stability of PNA makes it an ideal candidate for the antisense and antigene application. PNA is used as probe for gene cloning, mutation detection, and in homologous recombination studies. It was also used to design transcription factor decoy molecules for target gene induction. Morpholino, another structural type, was devised to circumvent cost problems associated with DNA analogs. It has become the premier knockdown tool in developmental biology due to its cytosolic delivery in the embryos by microinjection. Thus, the nucleic acid analogs provide an advantage to design and implementation, therapies, and research assays, which were not implemented due to limitations associated with standard nucleic acids chemistry.

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Designed guanidinium-rich amphipathic oligocarbonate molecular transporters complex, deliver and release siRNA in cells

“…This problem is further exacerbated by siRNA's susceptibility to enzymatic degradation (i.e., RNases) (3). To address these problems, two strategies have been pursued: development of noncharged and nonbiodegradable siRNA surrogates (10) and, more directly, development of delivery vehicles and strategies that would enable or enhance the entry of siRNA itself. Several siRNA delivery technologies have been reported thus far, including direct covalent conjugation of siRNA to lipids, peptides, or to aptamers; and noncovalent complexation of siRNA with polymers, biopolymers, nanotubes, lipid-based vehicles (e.g., lipopolyplexes, stable nucleic acid lipid nanoparticles), cyclodextrin polymer-based nanoparticles, fusion proteins, membrane translocation-modified magnetic nanoparticles, and antibodyprotamine conjugates (4,6,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22).…”