Novel Antisense and Peptide Nucleic Acid Strategies for Controlling Gene Expression

Abstract

Antisense oligonucleotides have the potential to make revolutionary contributions to basic science and medicine. Oligonucleotides can bind mRNA and inhibit translation. Because they can be rapidly synthesized to be complementary to any sequence, they offer ideal tools for exploiting the massive amount of genome information now available. However, until recently, this potential was largely theoretical, and antisense experiments often produced inconclusive or misleading outcomes. This review will discuss the chemical and biological properties of some of the different types of oligomers now available and describe the challenges confronting in vitro and in vivo use of oligonucleotides. Oligomers with improved chemical properties, combined with advances in cell biology and success in clinical trials, are affording powerful new options for basic research, biotechnology, and medicine.

Synthetic Genomics and Synthetic Biology Applications Between Hopes and Concerns

“…Finally, XNAs can show increased stability compared to DNA and RNA; 1,5-anhydrohexitol nucleic acids (HNA) and locked nucleic acids (LNA), for instance, were described to be not susceptible to biological nucleases [114,115]. In combination with the stable interaction of certain XNAs with DNA and RNA, which can experimentally and therapeutically be exploited to inhibit gene expression in various ways [116,117], potential effects on native organisms related to increased XNA stability might be worth considering.…”

Structure - Functions Relations in Small Interfering RNAs

“…Unlike antisense oligodeoxyribonucleotides (ODN), whose efficacy of action is determined by the efficacy of ODN hybridization with mRNA-target ( fig. 3) [42], the formation of the duplex between the "guide" strand of siRNA and mRNA-target occurs due to the helicase activity of RISC* and virtually independent from the hybridization properties of the oligoribonucleotide [43]. Silencing of gene expression by siRNAs is observed at the much lower ON concentrations than in the case of antisense ODN (IC50 for siRNAs is 100 -1000 times lower, than IC50 for antisense ODNs) [43,44].…”

Purification and assembly of thermostable Cy5 labeled γ-PNAs into a 3D DNA nanocage

“…11 Applications have been recently reviewed 12 including a review focused on chemical modifications to PNA. 13 Its synthetic backbone makes it highly resistant to nucleases and proteases 14 and useful for targeting DNA 15 and RNA, 16 as well as using it as a molecular probe 17 and biosensor. 18,19 PNA has also been assembled within DNA scaffolds to investigate applications in bionanotechnology.…”