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 parties.
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 nucleic acids.
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, etc.
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 have been reported to have good RNA specific binding affinity. Nevertheless, the enzymatic resistance is significantly lower than that obtained by the PS oligonucleotides and 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 offers:
BNA oligonucleotide can also be use in
Visit our tech lounge for more technical information.
Reference/Citing:
Visit our literature vaults for more references and citings.