As a leading CRO, BOC Sciences has been supporting customers at the forefront of drug conjugation. Protein-antibody conjugate (PAC) is an emerging technology used for targeted drug delivery that combines two different approaches, biologics and antibody-drug conjugates (ADC), to ensure precise and effective delivery of drugs to specific cells. We provide protein-antibody conjugation services to meet your unique project needs. Our scientific team will work with you to create a scope of work to complete the project on time and within specifications.
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The development of protein-antibody conjugates (PACs) has enabled targeted cellular delivery of biologics therapeutic proteins via antibodies. Inspired by ADCs, PACs consist of targeting units (antibodies), and therapeutic cargos (biological drugs). The biological drugs are produced from living organisms or contain components of living organisms, which may include carbohydrates, proteins, or nucleic acids or complex combinations of these substances. The biologics, building block of PACs, primarily refer to therapeutic proteins that can be used directly as therapeutic agents to directly address cellular functional defects. However, biologics primarily target extracellular defects, such as insulin therapies. The development of PACs has expanded the range of applications of biologics and greatly influenced cancer therapy as they selectively ferry biological drugs that are covalently attached to targeting antibodies to cancer cells.
Antibody-directed targeted delivery of proteins to specific cells takes advantage of the key advantages of ADCs and biologics. Similar to ADCs, proteins can simply bind to antibodies as fusion proteins, but this approach may have the limitation of a low ratio of drug to antibody. In addition, nanoparticles can be used to covalently bind antibodies and proteins.1 Because both the targeting antibody and protein cargo are large hydrophilic proteins, precise design of the assembly site is required. The antibody must be decorated on the surface of the nanoparticle, while the cargo protein must be present on the inside so that it cannot be reached by degrading proteases. The covalent attachment of antibodies or proteins to nanoparticles can be performed during the construction of PACs using bioorthogonal reactions such as the strain-promoted alkyne-azide cycloaddition (SPAAC).
The advantages of PACs:
Fig. 1 Construction of PACs. (Liu, 2021)
In order to realize the full potential of protein therapies, effective intracellular delivery is required. Current protein delivery methods generally suffer from low tolerance to serum, poor endosomal escape and limited in vivo efficacy. Loading therapeutic proteins onto antibodies to generate protein-antibody conjugates allows effective delivery of proteins to target cells. The design and construction of PACs has greatly expanded the range of applications for biologics, including cancer therapy, regenerative medicine, gene editing, and subunit vaccines.