Creative Biolabs can assist customers’ intrabody research through our professional library construction service. Our scientists are committed to offering our customers with impeccable scaffold library construction platform exploiting cutting edge technology and our long-term experience.
Intrabody is immunoglobulin or protein scaffold that specific targeting intracellular agents. As a majority of full length antibodies or scaffold domains have been developed against extracellular or cell surface targets, engineered intrabodies have gained extensive attention recently, due to their therapeutic potential. It can be applied in enormous fields in particular the therapy for tumor antigens, transplantation, infectious diseases, protein mutation-associated diseases and protein aggregation diseases. The mechanisms involved for therapeutic intrabody intervention include: regulating protein function, such as targeting α-synuclein to prevent aggregation; hindering protein interactions; accelerating protein degradation through conjugation of a proteasome target sequence; altering target protein subcellular localization or promotion of cell death for targeting cancerous cells. However, intrabody needs to circumvent the difficulty of intracellular delivery in therapeutic applications. In order to deliver intrabody into cells, avoid renal elimination and enhance serum half-life, some intracellular transport tags have been introduced. Alternatively, fusing to cell surface markers or conjugating with protein transduction domains (PTDs) are also methods for the same purpose.
Up to now, intrabody construction has been mainly leaning towards scFv and Fab fragments, especially camelid VHH domains or single domain antibodies. While, other protein scaffolds have also been considered or proven as more effective intrabody candidates rather than only immunoglobulin domains. On the basis of features such as solubility, stability, expression and function within the reducing environment of the cytoplasm, engineered protein scaffolds based on their various features may indicate more advantages than immunoglobulin domains to be qualified as intrabodies. In addition, combining with our well-recognized phage display technology, Creative Biolabs is able to generate a mass of accessible intrabody libraries to meet our clients’ demands.
Creative Biolabs has built scaffold libraries through our proprietary Hi-Affi™ phage display platform. The platform is based on phage display technology, which has become a major approach in selecting highly specific scaffolds. In phage display, the library of interest is fused to bacteriophage coat proteins and thereby displayed on the phage surface; the pool of phages is mixed with an immobilized target to isolate specific binders. Devised to expand the range of applications of specific protein scaffolds, our scientists have also integrated the trimer codon technology and NNK methods which introduce random mutations to expand the range of the library diversity. Therefore, Creative Biolabs can obtain 100% precise mutant library construction with over 1010 diversity for the generated scaffold libraries.
With years of research and development experience in the field of phage library construction, Creative Biolabs leads an elite team of experts who focus on the library construction and protein scaffold research. We have successfully generated 55 kinds of scaffold libraries for our customers all over the world. Creative Biolabs guarantees the reliability of each service through our strictly controlled quality standards.
Fig.1 Crystal structure of HRAS(G12V)-anti-RAS Fv (disulfide free mutant) complex. (PDB ID: 2VH5)