Tuesday, September 28, 2010

Lipid Oligonucleotide Conjugates

The availability of synthetic nucleic acids oligonucleotides and peptides, areas where BioSynthesis has extensive experience, has promoted the development of conjugates of these molecules cross-linked to compounds such as lipids, carbohydrates and small molecules (drugs) to yield products with distinct properties.

Lipid-oligonucleotide Conjugates
The main objective of cross-linking a lipid moiety to an oligonucleotide, either an oligodeoxynucleotide (ODN) or oligoribonucleotide (ORN), is to increase the hydrophobic character of the latter and its lipid-solubility. This way a conjugate would pass across the highly lipophilic cell membrane and into the cytosol, a process called transduction. Yet, depending on the lipid’s nature these conjugates may have also some other new biological properties.

Peptide-oligonucleotide Conjugates
Peptide-oligonucleotide conjugates have two moieties: a peptide that is covalently linked to an oligonucleotide: either an oligodeoxyribonucleotide (ODN) or an oligoribonucleotide (ORN). Alternatively, an oligonucleotide can be replaced with a bridged nucleic acid (BNA) that mimics the biological activity of that oligonucleotide. The oligonucleotide can interact with specific cell receptors to stimulate or inhibit biological responses, e.g. inhibition of a gene expression.

Carbohydrate-oligonucleotide Conjugates
These conjugates can have the carbohydrate moiety linked directly to the oligonucleotide or can be linked to a lipid or a peptide/protein. Due to the diversity of carbohydrate receptors present on the cell’s surface, oligosaccharides are useful for targeting conjugates to specific cells. Conjugation of antisense ODNs to a neoglycoprotein in which the protein has several mannose-6-phosphate residues, is readily internalized by cells having a receptor for this ligand on their surfaces.

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