Anti-pcna nanobodies, fusion proteins, and uses thereof

Abstract

The present disclosure provides anti-PCNA nanobodies, fusion proteins comprising the same, and uses thereof, which belong to the field of biotechnology. In the present disclosure, artificial intelligence technology is employed to design nanobodies that specifically target PCNA. The nanobodies exhibit favorable specificity and high affinity, and are capable of efficiently binding to the PCNA antigen. Further, rational design of the nanobodies via artificial intelligence technology yields nanobody mutants with higher affinity. Moreover, fusion proteins are prepared by fusing the aforementioned nanobodies or nanobody mutants with an RBCC domain or its mutant. The fusion proteins can specifically bind to a target protein via their nanobody domains, thereby initiating a protein degradation pathway to achieve targeted degradation of PCNA protein, and they can also activate intracellular p53, inducing its phosphorylation to prevent ubiquitination-mediated degradation by ubiquitin ligases such as MDM2, demonstrating significant clinical application value.

Dependencies are inferred from the claim text.