These proteins can be tailored to have specific biological properties.
A group of collagenlike recombinant proteins containing high densities of biologically active sites has been invented. The method used to express these proteins is similar to a method of expressing recombinant procollagens and collagens described in U. S. Patent 5,593,859, “Synthesis of human procollagens and collagens in recombinant DNA systems.”
Customized collagenous proteins are needed for biomedical applications. In particular, fibrillar collagens are attractive for production of matrices needed for tissue engineering and drug delivery. Prior to this invention, there was no way of producing customized collagenous proteins for these and other applications. Heretofore, collagenous proteins have been produced by use of such biological systems as yeasts, bacteria, and transgenic animals and plants. These products are normal collagens that can also be extracted from such sources as tendons, bones, and hides. These products cannot be made to consist only of biologically active, specific amino acid sequences that may be needed for specific applications.
Prior to this invention, it had been established that fibrillar collagens consist of domains that are responsible for such processes as interaction with cells, binding of growth factors, and interaction with a number of structural proteins present in the extracellular matrix. A normal collagen consists of a sequence of domains that can be represented by a corresponding sequence of labels, e.g., D1D2D3D4. A collagenlike protein of the present invention contains regions of collagen II that contain multiples of a single domain (e.g., D1D1D1D1 or D4D4D4D4) chosen for its specific biological activity. By virtue of the multiplicity of the chosen domain, the density of sites having that specific biological activity is greater than it is in a normal collagen. A collagenlike protein according to this invention can thus be made to have properties that are necessary for tissue engineering.
For example, deoxyribonucleic acid (DNA) encoding the D4 domain has been used to create a DNA construct that encodes for a collagenlike protein that consists of multiples of the D4 domain. From previous research, it was known that the D4 domain is critical for interaction of collagen II with chondrocytes. Hence, this multiple-D4 protein is superior to natural collagen for use as a scaffold material for repair of cartilage or for growth of cartilage in vitro.
This work was done by Andrzej Fertala of Thomas Jefferson University for Johnson Space Center.
In accordance with Public Law 96-517, the contractor has elected to retain title to this invention. Inquiries concerning rights for its commercial use should be addressed to:
Thomas Jefferson University,
Dermatology and Cutaneous Biology
BLSB/Room 424, 233 South 10th Street
Philadelphia, PA 19107
Refer to MSC-24151-1, volume and number of this NASA Tech Briefs issue, and the page number.