The present invention relates to polynucleotides comprising a Factor IX nucleotide sequence, wherein the Factor IX nucleotide sequence comprises a coding sequence that encodes a Factor IX protein or fragment thereof and wherein a portion of the coding sequence is not wild type. The present invention further relates to viral particles comprising a recombinant genome comprising the polynucleotide of the invention, compositions comprising the polynucleotides or viral particles, and methods and uses of the polynucleotides, viral particles or compositions.

A2M polypeptide compositions containing a non-natural bait region are disclosed. Methods of producing wild-type and variant A2M polypeptides and polynucleotides containing a non-natural bait region are also disclosed. The bait regions of the variant A2M polypeptides demonstrate enhanced protease inhibitory characteristics compared to wild-type A2M. Variant A2M polypeptides that demonstrate longer half-lives upon administration to an organism compared to wild-type A2M are disclosed. The A2M compositions are useful in treating a number of diseases and conditions including inflammation, chronic wounds, and diseases with a pathology associated with proteases.

Systems and methods for purification and concentration of autologous alpha-2-macroglobulin (A2M) from whole blood are provided. Also provided are diagnostic methods for identifying sites in the synovial joints, spine, tendons or ligaments for treatment of pain, degeneration, or inflammation with autologous A2M. Methods for utilizing autologous A2M in combination with other autologous treatments (e.g. platelets and other growth factors) are provided in addition to combinations with exogenous drugs or carriers. Also provided is a method of producing recombinant A2M wild type or variants thereof where the bait region was modified to enhance the inhibition characteristics of A2M and/or to prolong the half life of the protein in joints and spine disc or epidural space.

Systems and methods for purification and concentration of autologous alpha-2-macroglobulin (A2M) from whole blood are provided. Also provided are diagnostic methods for identifying sites in the synovial joints, spine, tendons or ligaments for treatment of pain, degeneration, or inflammation with autologous A2M. Methods for utilizing autologous A2M in combination with other autologous treatments (e.g. platelets and other growth factors) are provided in addition to combinations with exogenous drugs or carriers. Also provided is a method of producing recombinant A2M wild type or variants thereof where the bait region was modified to enhance the inhibition characteristics of A2M and/or to prolong the half life of the protein in joints and spine disc or epidural space.

Systems and methods for purification and concentration of autologous alpha-2-macroglobulin (A2M) from whole blood are provided. Also provided are diagnostic methods for identifying sites in the synovial joints, spine, tendons or ligaments for treatment of pain, degeneration, or inflammation with autologous A2M. Methods for utilizing autologous A2M in combination with other autologous treatments (e.g. platelets and other growth factors) are provided in addition to combinations with exogenous drugs or carriers. Also provided is a method of producing recombinant A2M wild type or variants thereof where the bait region was modified to enhance the inhibition characteristics of A2M and/or to prolong the half life of the protein in joints and spine disc or epidural space.

The present invention discloses a method for separating and purifying 2-macroglobulin from Cohn Fraction IV precipitation, in which Cohn Fraction IV precipitation is treated by ammonium sulfate precipitation, zinc ion affinity chromatography, gel filtration, and ultrafiltration and concentration sequentially and thereby 2-macroglobulin is obtained finally. With the method provided in the present invention, purified 2-macroglobulin plasma protein that has a clinical application value is obtained, the Cohn Fraction IV precipitation is changed from a discarded material into a valuable material, and plasma is utilized comprehensively. In addition, the method is easy and simple to use, easy to scale up, and suitable for separation and purification of 2-macroglobulin at a large scale.

The present invention provides a peptide with sequence of DEAQETAVSSHEQD, a fragment of rabbit-1 antiproteinase F, and its derivatives DEAQETAVSSHEQ and QETACSSHEQD, which significantly inhibit serum-borne HCV replication in hADSC and human hepatocytes.

The present invention relates to proteinaceous prodrug constructs, e.g., proteinaceous fusion constructs that comprise a complement 3- and pregnancy zone protein-like, alpha-2-macroglobulin domain-containing (CPAMD) protein (e.g., A2M) and one or more drugs and function as protease-activatable prodrugs.

Systems and methods for purification and concentration of autologous alpha-2-macroglobulin (A2M) from whole blood are provided. Also provided are diagnostic methods for identifying sites in the synovial joints, spine, tendons or ligaments for treatment of pain, degeneration, or inflammation with autologous A2M. Methods for utilizing autologous A2M in combination with other autologous treatments (e.g. platelets and other growth factors) are provided in addition to combinations with exogenous drugs or carriers. Also provided is a method of producing recombinant A2M wild type or variants thereof where the bait region was modified to enhance the inhibition characteristics of A2M and/or to prolong the half life of the protein in joints and spine disc or epidural space.

A novel composition and method of enhancing wound healing and minimizing rejection of an implant is presented. The composition is a dry acellular mixture comprised of conditioned media from mesenchymal stem cells, a multifunctional protease inhibitor, and a tethering peptide that acts as a tether to keep the composition in contact with the targeted area. An antimicrobial fusion peptide may also be added to the composition.