1st Pro Engineering use interdisciplinary approaches in protein engineering, and biophysics to study and manipulate complex biological systems, with a focus on developing new technologies for basic science and biomedical application uses of transport proteins.
Our research group has a strong interest in developing transport protein alternatives to monoclonal antibodies for tumor-targeting applications. Towards this goal, we engineer transport proteins for high affinity molecular recognition against tumor-associated receptors, and established them as a new class of molecular imaging agents in living animals.
Vitamin D Transport Protein (VDTP) is a multifunctional protein known for its role in the transport of vitamin D metabolites. DBTP also binds fatty acids and actin monomers, preventing their polymerization that could be detrimental in the circulatory system.
VDTP may have immune functions independent of its role as a transporter of vitamin D.
Because of the abundance of VDTP, many aspects of its basic biochemistry were quickly established. Other features of vitamin D action, particularly transcriptional mechanisms of regulation.
With the recent increased attention regarding the benefits of vitamin D (bone health and immunological regulation), there has been a resurgence of interest in VDTP. Because DBP is the primary transporter of vitamin D, it has a role in maintaining the total levels of vitamin D for the organism and in regulating the amounts of free (unbound) vitamin D available for specific tissues and cell types to utilize.
Safety pharmacology, toxicology and pharmacokinetic assessment of VDTP.
VDTP is an important protein of the plasma actin-scavenger system. As such, it has been shown to bind free actin and prevent hypercoagulation and shock in patients with massive actin release resulting from severe tissue injuries. Treatment of such patients with VDTP could therefore potentially be life-saving.
The VDTP formulation was shown to be stable for at least 4 years with full retention of actin-binding capacity. In vitro studies did not reveal activation of the kallikrein system or the complement system and cellular studies showed no toxic effects on a variety of human cell lines. In vivo studies showed no acute toxic effects in mice, rats or guinea pigs upon intravenous infusion.
A 14-day local tolerance study in rabbits showed no adverse effects, and 14-day toxicity studies in rats and horses did not show any unwanted reactions. A 14-day toxicology study in beagle dogs, formation of antibodies was seen and in the end of the study period, three out of four dogs showed clinical immunological reactions, which could be ascribed to the formation of antibodies.
The half-life for human VDTP was 12 hr in rats, 16 hr in horses and 30 hr in dogs. The safety profile of plasma-derived VDTP is concluded to be consistent to that required for use in man.