Chaperones are PEGylated liposomes which may be used by themselves and applied either topically or subcutaneously to escort (“chaperone”) endogenous proteins and peptides (the Agent of Interest) in the body to extend their kinetics.
The liposomes use polyethyleneglycol (PEG) tethered to the head group of a fatty acid chain that itself is embedded in the wall of the vesicle. The PEG provides some very useful attributes to the Chaperone vesicle, in particular it cloaks the vesicle in a sphere of water, meaning the Chaperoned protein or peptide has a longer half life in the body, extending dosing intervals, reducing dosing amounts, and saving costs. In addition, the presence of PEG can allow for a change of administration from intravenous to subcutaneous as previously “sticky” proteins or peptides become water covered and less sticky Chaperoned AOIs.
The PEG is tethered to the surface of the liposome via a carefully-chosen functional group that not only provides for the covalent attachment of PEG but also provides a very useful anchoring site. Certain proteins that have a particular sequence of amino acids (a consensus sequence) within their structure have a natural affinity for this functional group.
This facilitates strong non-covalent bonding between the Chaperone and the AOI. The strength of this affiliation is normally expressed in terms of an on/off ratio, where the molecules are assessed and measured to see what percentage of time they are pressed against each other at the target site of the AOI (on) and the percentage that they are not (off). Pro Bono Bio has developed Chaperoned AOIs with an on/off sequence as high as 80/20. This means that, even when they are “off” they are very close to each other.
Careful selection of the right site on the AOI molecule means that the functionality of the Chaperoned AOI is unimpaired. Additionally it is possible to use the Chaperone to cover problematic epitopes on the surface of the AOI, which otherwise cause undesirable immune reactions within a patient group.
The benefits provided by Chaperoning are that unchanged and proven AOIs can be delivered and sustained in the body so that dosing, administration and cost benefits are achieved without having to characterise and develop a new chemical or biological entity. Regulators, payors, physicians and patients can all rely on the established safety profile of an existing treatment that has simply been made to work better.