Development of artificial nucleic acids is essential for the design of new efficient
tools for molecular biology as diagnostic probes or the design of potentially new
drugs for oligonucleotide-based therapies. Of particular interest are artificial
nucleic acids with the following characteristics:
As a pioneer in oligonucleotide synthesis, Bio-Synthesis Inc. has been pursuing
the development of new oligonucleotide based technologies that can provide compounds
that have superior binding affinity and chemical/biological stability. As such,
Bio-Synthesis Inc. is introducing its third generation Bridged Nucleic Acids
(BNA) . This new technology is based on multi-functional synthetic
RNA analogues that can be used in place of the first generation bridged nucleic
acids known as Locked Nucleic Acids (LNA). These RNA analogues can be synthesized
and spiked with DNA or RNA in order to modify the formation of nucleic acid helices.
Also, when compared to Peptide Nucleic Acids (PNA), BNA allows for better base-pair
stacking and a high stability of the resulting oligonucleotide complexes, making
BNA based oligonucleotides an ideal solution for the detection of small or highly
similar DNA or RNA targets.
Bio-Synthesis Inc. is now providing synthetic oligonucleotides containing BNA which
are deprotected, desalted or HPLC purified. All oligonucleotides are quality checked
by MALDI-TOF Mass Spectrometry.
BNA oligonucleotides exhibit significantly higher affinity to their complementary
strands when compared to previous generations of constrained nucleic acids (PNA
& LNA). Their extraordinary level of sensitivity, specificity for nuclease-resistant
activity, makes these multi-functional BNA nucleic acids a superior tool for developing
high value detection systems and therapeutic products
Bio-Synthesis, home of BNATM oligonucleotides
Bio-Synthesis under a licensing agreement with BNA Inc, is the exclusive provider
of synthetic BNAs; purchase of research use of BNA’s only, carries a research use
only license; clinical/therapeutic and/or commercial applications of BNA’s required
a separate commercial license; we will be glad to discuss licensing terms with interested
Natural nucleic acids have a higher degree of freedom in their chemical structure.
This feature is thermodynamically unfavorable for DNA-DNA and RNA-RNA double strand
formation (hybridization) and is often subject to degradation by both endo and exonucleases.
Improving binding affinity (hybridizing capability) is yet unresolved for highly
sensitive gene-targeting applications.
Bridged nucleic acid 2',4'-BNANC (2'-O,4'-aminoethylene bridged nucleic
acid) RNA analogue, containing a six-member bridged structure with an N-O linkage,
was developed by Professor Emeritus Takeshi Imanishi of Osaka University. These
novel nucleic acid analogues can be synthesized and incorporated into oligonucleotide.
When compare to the earlier generation of 2', 4' BNA (LNA)- modified oligonucleotides,
2', 4'-BNANC [N-Me] analogues were found to possess:
2',4'-BNA(NC)-modified oligonucleotides with these excellent profiles show great
promise for applications in antisense and antigene technologies.
These nucleic acid analogs can be easily incorporated into natural oligonucleotide
strands. They provide flexibility in designing BNA/DNA and BNA/RNA hybrid oligos
to satisfy the need for very high and sequence-specific hybridization with natural
nucleic acids. Additionally, they possess a strong nuclease-resistant property.
While first generation BNA (also known as LNA) is still used in various applications,
Bio-Synthesis Inc. now offers third generation, six member bridged 2', 4' BNANC
which has shown to possess superior properties to the earlier generation of locked
BNA oligos allow greater flexibility in the design of primers and probes. They can
be mixed with DNA, RNA and other nucleic acid analogs using standard phosphoramidite
synthesis chemistry. BNA oligonucleotides are also easily labeled or modified with
standard oligonucleotide tags such as DIG, fluorescent dyes, biotin, amino-linkers,
For additional information please contact us
BNA can be mixed with DNA, RNA and other nucleic acid analogs within the oligonucleotide
to facilitate changes of Tm (melting temperature) without losing specificity. They
allow for shorter probe design while maintaining the same Tm. The Tm of a nucleotide
duplex can be modulated by varying the BNA content. This feature can be used to
normalize the Tm across a population of short sequences with varying GC-content.
For AT-rich nucleotides with low melting temperatures,
The addition of BNA can be used to raise the duplex Tm. This enables the design
of BNA oligonucleotides with a narrow Tm range, which is beneficial in microRNA
research, PCR, microarray and applications where hybridization sensitivity and specific
binding to many different targets must occur under the same condition.
Older generations of 2',4'-LNA do not posses sufficient resistant to nuclease, nor
the flexibility required for efficient triplex formation. The increased duplex and
triplex-forming ability of BNA conforms with the Watson-Crick binding and gives
BNATM oligonucleotides a high binding affinity to ssRNA and dsDNA. This
strand invading property makes BNATM an excellent tool for in vivo applications.
Incorporating BNA into oligonucleotides, further enhanced resistance against nuclease
degradation and leads to high in vitro and in vivo stability, making BNANC
a promising therapeutic agent.
The physiological properties of BNA® such as water solubility are very similar
to those of DNA and RNA. BNA can therefore be easily adapted to conventional experimental
protocols. It can be incorporated with most oligonucleotide synthesis chemistries
and analysis methods.
Although siRNA elicit RNAi activity in cell culture, their in vivo usage as a drug
remains questionable because of low biostability and undesirable toxicity (off-target
effects). The effort to use nucleotide analogues to overcome these problems and
to improve pharmacokinetics and delivery of siRNA are increasing daily. Example
of using Locked Nucleic Acids (LNA), 1st generation of Bridged Nucleic Acids has
been reported to have good RNA specific binding affinity. Nevertheless, the enzymatic
resistance is significantly lower than that obtained by the PS oligonucleotides,
the consecutive LNA bases, and fully modified LNA analogue are very rigid, resulting
in inefficient triplex formation. Peptide nucleic acids (PNA) also possessed promising
RNA selective binding affinity. However, their mode of RNA targeting was achieved
via triplex formation, which requires the use of two folds of antisense nucleic
acids. In addition to that, PNA has limited aqueous solubility, poor cellular uptake
and ambiguity in binding complementary DNA/RNA in both parallel and antiparallel
orientations. Several reports have shown that nucleotide analogue 2', 4'-BNA NC
is substantially compatible with the in vivo siRNA or antisense technology. siBNANC
BNA oligonucleotide can also be use in
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