Avidin Fusion Protein Strategies in Targeted Drug and Gene Delivery

Abstract

Chicken avidin is used in a wide variety of applications in the life sciences, due to its extraordinarily strong affinity for biotin. Avidin-biotin strategy has also recently established a role in medical targeting approaches for cancer treatments. An interesting new exploitation for avidin-biotin techniques is the utilization of this strong affinity in gene therapy, to target and enhance gene delivery to the appropriate target cells and tissues. In this communication, we review novel avidin fusion proteins that have been developed for enhanced gene delivery and drug targeting purposes. The principles of this approach are highlighted by the avidin fusion proteins Scavidin (fusion with the macrophage scavenger receptor class A), Lodavin (fusion with the endocytotic LDL receptor) and avidin-displaying baculovirus (Baavi). Scavidin and Lodavin are cell membrane proteins in which avidin is expressed as an extracellular portion, thereby enhancing the targeted drug and gene delivery with biotinylated drug molecules and vectors. Baavi, on the other hand, displays avidin moieties on its surface, and opens up possibilities for flexible modification of its targeting properties and other characteristics by using different biotin-conjugated molecules. Potential applications of avidin fusion proteins and future trends of targeted drug and gene delivery based on these strategies will be discussed.

Targeted delivery of proteins by nanosized carriers

“…Chemical modifications of targeting proteins often damage their ability to bind cellular targets, yield heterogeneous preparations, and require custom development. To overcome these issues, several authors exploited the strong interactions between biotin and avidin, 64 a chicken protein with four biotin binding sites (Fig. 4).…”

Bacterial avidins are a widely distributed protein family in Actinobacteria, Proteobacteria and Bacteroidetes

“…The first known avidin was isolated from the chicken ( Gallus gallus ) egg white in 1941 [ 1 ] as a minor protein component showing extremely high avidity to biotin (K d ≈ 10 −15 M) and is a text-book example of tight protein–ligand interaction [ 1 , 2 ]. This combined with the avidin’s compact tetrameric structure with four biotin-binding sites in each functional protein, and the existing methods to biotinylate a vast variety of biomolecules, has made avidin an important biotechnological tool in protein purification, detection, and assay technologies, but also in diagnostics and pharmaceuticals [ 3 , 4 ].…”

A Streptavidin−Protein Cage Janus Particle for Polarized Targeting and Modular Functionalization

“…Attempts to use a symmetrically biotinylated protein-cage nanoplatform for StAv coupling resulted in extensive cross-linking and aggregate formation, as expected. Although StAv can be covalently linked to biomolecules, the substantial effort directed at creating StAv chimeric fusion proteins suggests that this route is labor-intensive for many protein−StAv pairs. , Furthermore, our strategy of using toposelectively biotinylated nanoplatforms as the starting material not only facilitates coupling of StAv to the nanoplatform but also enables a measure of control over the stoichiometry of the coupling. Thus, the final nanoplatform is sufficiently functionalized for targeting while leaving many addressable sites available for designing functional activity or cargo transport into the system.…”