These novel DNA modifications are said to be the first in 20 years to demonstrate all of the desired properties for antisense gene silencing using DNA fragments
MetaSense Technologies has announced the publication of the first biochemical, biophysical, and biological studies on a set of two new DNA analogues in the journal Nucleic Acid Research (31 (14), 4109-4118, 2003).
These novel DNA modifications, phosphonocarboxylates, are said to be the first in 20 years to demonstrate all of the desired properties for antisense gene silencing using DNA fragments.
Since the introduction of antisense technology almost two decades ago, few if any DNA analogues have shown such a remarkable combination of desirable properties.
Biochemically, these new DNA analogues were shown to hybridise to complementary RNA molecules in a sequence specific manner, were highly nuclease resistant, and RNase H active. Specific constructs of these analogues were shown to have greatly enhanced rates of RNase H cleavage, even over the natural DNA/RNA substrates.
Biophysically, these DNA analogues when hybridised to complementary RNA gave structures highly analogous to natural DNA/RNA duplexes.
Biologically, specific constructs were shown to readily penetrate cell membranes.
The publication was submitted by the laboratory of Distinguished Professor Marvin H Caruthers from the University of Colorado, Department of Chemistry and Biochemistry.
"The data generated to date on these analogues has been truly remarkable; so is the interest that they are generating in the research community.
"Our goal is still to get these new tools into the hands of researchers quickly, we have great confidence in what will result" said Dirk Dellinger, president of MetaSense Technologies, the corporation exclusively licensed to sell reagents to make oligo.
"Today, the field of gene silencing is becoming a very exciting and revolutionary place.
"Whatever technique is used (antisense or RNAi) an intact (stabilised), active molecule is required to penetrate the cell; from the recent data generated we believe that phosphonocarboxylates will play a significant role in the future of these technologies." he concluded.
"We never expected such astonishing data to be generated so quickly. "The key appears to be in developing good phosphorus chemistry that resulted in desired properties and behaviors," stated Professor James G Lindberg, chief technology officer for MetaSense Technologies.
"I believe that the ability to quantitatively couple phosphonocarboxylates to any biological molecule has even broader implications beyond gene silencing (antisense, RNAi, or gene therapy), and into phosphopeptides or small molecule therapeutics.
"Although I can't predict the future, I can't wait to see the results of further investigations," he remarked.
