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BsAb Application in Gene Therapy

Based on years of experience in bispecific antibody (BsAb) engineering, Creative Biolabs provides unparalleled BsAb services that can greatly facilitate your scientific and clinical research.

Gene therapy refers to the therapeutic approach in which genes are transferred into patients’ cells for therapeutic purposes. In gene therapy, human genes can be transferred for gene correction to cure inherited diseases, while introduction of therapeutic genes from various species can benefit the treatment of many diseases. Gene therapy drugs consist of a therapeutic gene and a gene transfer vector while an adapter molecule that directs the vector to target cell and mediates cell entry of the therapeutic gene is also needed. The gene transfer vector and adapter can be manipulated and thus the therapeutic gene expression can be permanent or transient, constitutive or inducible, ubiquitous or targeted, based on the demand. In gene therapy, a BsAb can be used as the therapeutic gene being transferred or developed as an adapter molecule.

Direct and cell-based gene delivery. (Collins, M., 2015)

Figure 1. Direct and cell-based gene delivery. (Collins, M., 2015)

BsAbs as Adapter Molecules

A BsAb can be developed as an adapter molecule to recognize the vector and a specific marker on target cell surface. Adopting BsAbs as adapter molecules has several advantages. First of all, this method does not require modifications of the virus and avoids disruption of vector assembly, stability, or activity. Secondly, genetic, biological and chemical approaches are well developed for BsAb engineering. One can design specific BsAbs to bind almost any two receptors/epitopes/proteins. What’s more, an established target cell-BsAb-vector system is capable of delivering any other therapeutic gene to the target cell. Most BsAbs investigated as adapter molecules are for adenoviral (Ad) vectors. One fragment of the BsAb binds to Ad capsid proteins while the other one binds to the cell surface target molecules. Bispecific IgGs, tandem scFvs or single-chain diabodies produced by genetic engineering, chemical conjugation or genetic fusion (hybrid-hybridoma) are some commonly used BsAbs for this purpose. These BsAbs can bind various antigens, including CD40, EpCAM, CD70, Tag72, and ACE, and have been applied to mediating Ad gene transfer to various cell types.

Therapeutic BsAb Delivery by Gene Therapy

Alternatively, a gene that encodes a therapeutic BsAb can be the therapeutic gene that is transferred through gene therapy. BsAbs are important therapeutic proteins. In some cases, gene therapy is exploited for expressing BsAbs in patients to achieve efficient antibody concentration at desired localization. Since gene therapy allows for local expression of the therapeutic BsAb, it overcomes problems such as rapid antibody clearance or poor access to tumors. Gene therapy possesses flexibility and high potential for improving antibody delivery for specific applications.

This figure shows the scFv structure and recombinant adeno-associated virus (rAAV) delivery of scFv. (Huang, L., 2013)

Figure 2. This figure shows the scFv structure and recombinant adeno-associated virus (rAAV) delivery of scFv. (Huang, L., 2013)

Creative Biolabs is unparalleled in BsAb service in the world. Creative Biolabs possesses superior BsAb production platforms and a well experienced research team. Versatile BsAb with high sensitivity and reproductively are available and will facilitate you research.

References

1. Collins, M.; Thrasher. A. Gene therapy: progress and predictions. The Royal Society. 2015, 282(1821): 20143003.
2. Huang, L.; et al. Single-chain fragment variable passive immunotherapies for neurodegenerative diseases. International journal of molecular sciences. 2013, 14(9): 19109-19127.

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