Thursday, March 24, 2011

Lipid Oligonucleotide Conjugates

The availability of synthetic nucleic 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.


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 peptidonucleic 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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