Research Interest
1. Antibody discovery and preparation
2. Targeted therapy
3. Tissue engineering materials
Research Fields
1. Develop rapid and new nanobody preparation technology; establish nanobody-based enzyme-linked immunoassay, chemiluminescence, electrochemiluminescence and other detection technology platforms; develop high-sensitivity diagnostic technology for early diagnosis of malignant tumours, chronic metabolic disease and infectious diseases; develop nanobody-based targeted drug screening, design and controlled-release, reveal its function and mechanism at the molecular level, provide new insights for clinical treatment of major diseases.
2. Develop multifunctional and high-performance protein materials; obtain various high value-added protein materials (eg, collagen, spider silk protein, mussel adhesion protein, elastin, etc.) by bioengineering and molecular biology technology; develop and synthesize tissue substitute materials, controlled-drug release carriers, biological dressings and tissue adhesives by material science and polymer chemistry.
Representative Research
1. The Development of Rapid and New Nanobody Preparation Technology
The laboratory has established the complete nanobody preparation technology, including antigen preparation, alpaca immunization, nanobody screening and affinity analysis. Based on this technology, research group has obtained nanobodies with nM affinity against a variety of tumor markers, such as carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), human epididymis protein 4 (HE4), alpha fetoprotein (AFP).
2. The Development of New Chromatography Separation Technology for tag-free nanobody
The laboratory has established a simplified, seamless and non-affinity purification platform for the purification of a tag-free nanobody by void-exclusion anion exchange chromatography (VEAX) and multimodal weak cation exchange chromatography (Capto MMC). The entire two-step purification platform yielded nanobodies with a total protein recovery of 80.5% and the purity of 98.5%, which provides a competitive alternative for the conventional affinity chromatography antibody purification strategy.
3. The Development of Nanobody-based CEA Diagnostic Reagent
The laboratory has established a high-stability nanobody-based chemiluminescence enzyme immunoassay (CLEIA) kit for CEA detection. The CLEIA system has much better stability and linearity with similar reproducibility compared with the enzyme-linked immunosorbent assays developed from conventional monoclonal antibodies, which have been widely used in clinics over the past several decades.
4. Research on Targeted Drugs
Based on the nanobodies screened by the research team, nanobody-modified nanoparticles (e.g. silica nanoparticles, silk fibroin nanoparticles) for the targeted delivery of antineoplastic agent have been developed. The laboratory has also established hydrogels prepared from tilapia skin collagen and chitosan to encapsulate nanobodies and achieve their pH-responsive sustained release, which can be developed into an intelligent responsive tumor treatment matrix in cancer therapy.
5. Recombinant spider silk protein
Spider silk protein has attracted much attention in tissue engineering due to its high material properties and biocompatibility. Through the enhancement of engineering bacteria and and controlling the structure of spider silk protein, the research group obtained many kinds of water-solubilize recombinant spider silk protein through bioengineering method, with the highest molecular weight of ~250 kDa and the yield of ~1.5 g/L on the fermentor level.
6. Collagen composite material
Collagen has good biocompatibility and bioactivity, but its poor strength and stability limit its application in related fields. Through combining the interactive interpenetrating network system and spider silk protein,the research group obtained a series of reinforced collagen composite materials with high material strength and stability. In cytological experiment, the materials showed good biological activity, which could support adhesion and growth for variuos cell lines.
7. Tissue adhesive based on mussel adhesion protein
Through prokaryotic expression, in vitro modification and coacervate assembly, we obtained a tissue adhesive based on recombinant mussel adhesion protein. This adhesive could maintain tissue adhesive for a long time in humid environment (the adhesion force could reach 0.5 MPa), and has good biocompatibility.
8. Collagen like protein
By sequence simulation, we designed and obtained a collagen like protein which can be obtain through prokaryotic expression. Under suitable environment, this protein could quickly assembled into hydrogel with good strength, stability and bioactivity.
Contact
nianrui@qibebt.ac.cn
