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Vitamin-Mediated Cell Delivery of Oligonucleotides – an Attractive Approach for Therapeutic Applications

publication date: Jun 11, 2014
 | 
author/source: Link Technologies

Link Technologies Ltd, a specialist oligonucleotide reagent manufacturer, has announced the availability of a novel vitamin modifier, which has shown in initial tests to have the potential of improving cell delivery of oligonucleotides.

Phosphoramidite copyThe new reagent, 5’-Niacin-CE Phosphoramidite, is easily incorporated during solid phase oligo synthesis. The niacin-based modifier from Link offers several advantages over the use of conventional lipophilic delivery agents, including reduced risk of in vivo toxicity, and removes the necessity of cleaving the delivery reagent once in the cell. These benefits make vitamins, including niacin, an attractive method for the delivery of therapeutic oligonucleotides, such as siRNA, into cells.

While lipophilic modifier reagents have been shown to enhance cell penetration, vitamin-mediated cell delivery offers a distinct advantage due to the fact that vitamins are required, but not produced by cells. As such, it is believed that interaction with a specific binding protein is required before the vitamin-oligo conjugate is internalised. Not only does this enhance delivery and overcome the risk of toxicity, as the vitamin-based reagents are recognised by the cell, but it also offers some exciting potential for cell targeting.

Derived from niacin, an essential vitamin heavily involved in the biosynthesis of NAD and NADH, Link’s new vitamin modifier, 5’-Niacin-CE Phosphoramidite, is significantly less hydrophobic and less bulky than existing delivery agents. Whereas large lipophilic modifiers can supress an oligo’s function in vivo and therefore require cleaving, which is difficult to control, it is expected that with vitamin-based modifiers, intracellular cleavage of modifiers is not necessary. Potentially, this will lead to a reduction in required dosage of the therapeutic oligonucleotide, importantly minimising the risk of drug toxicity and side effects to the patient.

Catherine McKeen, Head of Technology Commercialisation, explained: “The ability to incorporate vitamin modifiers during oligo synthesis opens up significant potential to utilise a range of vitamin-oligonucleotide conjugates as a means of enhanced cellular uptake of therapeutic oligonucleotides.  5’-Niacin-CE Phosphoramidite is the second vitamin-based reagent in Link’s portfolio, alongside our tocopherol modifiers, and we will continue to add to this range.”

As an ISO 9001:2008 certified company, Link provides the novel modifier reagent in quantities ranging from milligramme to multi-gramme bulk scale, to support entire project life-cycles. Although protected by patent, Link is making this product available for purchase with an implied licence for research-use-only (RUO) applications, ensuring that the high potential of vitamin-mediated cell delivery can be easily accessed and validated in laboratories worldwide. To promote the uptake of the technology in commercial applications, Link welcomes approaches for such licences, and is committed to negotiating attractive terms to prospective commercial partners. 


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