HPMA copolymers for masking and retargeting of therapeutic viruses.
Hydrophilic polymers are widely used already for steric stabilisation of bioactive proteins, changing their pharmacokinetics and modifying their interactions with the biological environment. Polymers may also be conjugated to biological surfaces, such as viruses, bacteria and mammalian cells, also to endow steric protection and changed properties. Reactive polymers based on N-[2-hydroxypropyl]methacrylamide have shown particular promise for surface coating of viruses, particularly adenovirus, and here we describe the important observations and innovations arising from this combination of chemical and genetic engineering. Adenovirus is a versatile agent that already finds important experimental applications as a recombinant vaccine, and also for cancer therapy, although its activity in both settings is often limited by a potent antibody-neutralising response in humans that is generally not seen in experimental animals. Coating with HPMA copolymers provides protection against neutralisation by antibodies and complement, and covalent linkage of novel ligands to the surface of the polymer can endow new infectious tropisms, mediated through different receptors, that can expand the potential applications of this versatile technology for a range of settings.
Fisher
Kerry D
KD
University of Oxford, Department of Clinical Pharmacology, Old Road Campus Research Building, Old Road Campus, off Roosevelt Drive, Headington, Oxford OX3 7DQ United Kingdom.
Seymour
Leonard W
LW
D000178:Acrylamides / Q000008:administration & dosage* / Q000627:therapeutic use; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004337:Drug Carriers / Q000008:administration & dosage / Q000627:therapeutic use; D018390:Gene Targeting / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D050130:Oncolytic Virotherapy / Q000379:methods*; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry
D000178:Acrylamides; D004337:Drug Carriers; D011108:Polymers; C032976:N-(2-hydroxypropyl)methacrylamide