Affimer reagents enable targeted delivery of therapeutic agents and RNA via Virus-Like Particles

Monoclonal antibodies have revolutionised therapies, but non-immunoglobulin scaffolds are becoming compelling alternatives owing to their adaptability. Their ability to be labelled with imaging or cytotoxic compounds and to create multimeric proteins are attractive strategies for therapeutics. Focusing on HER2, a frequently overexpressed receptor in breast cancer, this study addresses some limitations of conventional targeting moieties by harnessing the potential of these scaffolds. HER2-binding Affimers were isolated and characterised, demonstrating potency as binding reagents and efficient internalisation by HER2-overexpressing cells. Affimers conjugated with cytotoxic-agent achieved dose-dependent reductions in cell viability within HER2-overexpressing cell lines. Bispecific Affimers, targeting HER2 and virus-like particles, facilitated efficient internalisation of virus-like particles carrying eGFP-encoding RNA, leading to protein expression. Anti-HER2 affibody or DARPin fusion constructs with the anti-VLP Affimer further underscore the adaptability of this approach. This study demonstrates the versatility of scaffolds for precise delivery of cargos into cells, advancing biotechnology and therapeutic research.