The invention is directed to
fibrin materials for use in
fibrin compositions and methods that avoid the need to use
thrombin as an activating agent for
fibrin monomer-based sealants. The invention provides for substantially pure fibrin chains, fibrin chain precursors, fibrin chains with other N-terminal extensions, fibrin
monomer, fibrin-homolog and fibrin-analog. The invention further provides for variant fibrin .gamma.-chains. The variant gamma-chain contains one or more mutations and / or deletions in the C-terminal region following the coiled-coil forming region such that, when incorporated into fibrin-homolog, the homolog lacks the ability to self-polymerize but has the ability to form non-covalent bonds, and thereby form mixed polymers useful as sealants, with
fibrinogen. The invention also provides
nucleotide sequences encoding fibrin chains or fibrin chain variants and cells expressing fibrin chains, fibrin chain variants, fibrin
monomer, fibrin precursor or
fibrinogen-analog. The invention further provides a method of forming fibrin-related proteins
in vitro from their component fibrin chains. The invention additionally provides a method for forming a fibrin
sealant by a reacting a first fibrin-related
protein that is incapable of self-polymerizing with a second fibrin-related
protein that is incapable of self-polymerizing.
Fibrin chains produced by methods of the present invention may be used as sources of substantially pure starting material for the production of important fibrin-derived factors that regulate
angiogenesis,
platelet aggregation, and other physiological processes.