Bridged nucleic acid

An increased conformational inflexibility of the sugar moiety in nucleosides (oligonucleotides) results in a gain of high binding affinity with complementary single-stranded RNA and/or double-stranded DNA.

These modifications allow to control the affinity towards complementary strands, regulate resistance against nuclease degradation and the synthesis of functional molecules designed for specific applications in genomics.

Yamamoto et al. in 2012[9] demonstrated that BNA-based antisense therapeutics inhibited hepatic PCSK9 expression, resulting in a strong reduction of the serum LDL-C levels of mice.

The findings supported the hypothesis that PCSK9 is a potential therapeutic target for hypercholesterolemia and the researchers were able to show that BNA-based antisense oligonucleotides (AONs) induced cholesterol-lowering action in hypercholesterolemic mice.

A moderate increase of aspartate aminotransferase, ALT, and blood urea nitrogen levels was observed whereas the histopathological analysis revealed no severe hepatic toxicities.

[citation needed] Application of BNAs include small RNA research; design and synthesis of RNA aptamers; siRNA; antisense probes; diagnostics; isolation; microarray analysis; Northern blotting; real-time PCR; in situ hybridization; functional analysis; SNP detection and use as antigens and many others nucleotide base applications.

The 3D structures for A-RNA and B-DNA
Chemical structures of other BNAs that were synthesized in the past years as indicated below the structures.
Chemical structures of BNAs were introduced in 2007 by Imanishi's group. [ 7 ] These new generation of BNAs analogues are called 2',4'-BNA NC [NH], 2',4'-BNA NC [NMe], and 2',4'-BNA NC [NBn].
Makoto Koizumi in 2004 reviewed the properties of BNAs with focus on ENAs as antisense and antigen oligonucleotides (AONs) and proposed an action mechanism for these compounds that may involve translation arrest, mRNA degradation mediated by RNase H and splicing arrest.