A method includes: depositing whole blood into at least one separator tube; subjecting the at least one separator tube to a first centrifugal force to cause a combination of the first centrifugal force and separator gel within each separator tube of the at least one separator tube to separate plasma of the whole blood from red and white blood cells of the whole blood within the at least one separator tube, wherein the plasma includes α2M molecules; transferring one or more portions of the plasma from within the at least one separator tube and into at least one isolator; and subjecting the at least one isolator to a second centrifugal force to cause a combination of the second centrifugal force and a filter within each isolator of the at least one isolator to isolate the α2M molecules from other components of the plasma within the at least one isolator.

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.

The present invention provides methods and compositions for reducing internalization and/or trafficking of tau in neuronal cells comprising contacting the cells with an effective amount of an LRP1 and/or SorLA antagonist. The invention further provides a method of treating or preventing Alzheimer's disease in a subject in need thereof, comprising administering to the subject an effective amount of an LRP1 and/or SorLA antagonist.

Hepatitis C virus (HCV) infection is a leading cause for liver cirrhosis and hepatocellular carcinoma worldwide.sup.2. Current therapeutic regimens are usually poorly tolerated and only effective in a proportion of infected individuals. We discovered a peptide with sequence of DEAQETAVSSHEQD (SEQ ID NO: 1), a fragment of rabbit α1-antiproteinase F, and its derivatives DEAQETAVSSHEQ (SEQ ID NO: 2) and QETAVSSHEQD (SEQ ID NO: 3), significantly inhibit serum-borne HCV replication in hADSC and human hepatocytes.

Systems and methods for purification and concentration of autologous alpha-2 macroglobulin (A2M) from whole blood and or recombinant A2M are provided. Also provided are methods of treating wounds with A2M. Methods for utilizing A2M in combination with other 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 for treating wounds.

Ecotin variants and their use in treating viral hemorrhagic fever are described. Described herein are methods for treating systemic inflammatory response syndrome or viral hemorrahagic fever by administering an ecotin polypeptide. Described herein is a polypeptide comprising the amino acid sequence of any of SEQ ID NOs: 2-9 and 11-18. Also described: is a polypeptide comprising the amino acid sequence of any of SEQ ID NO: 11-18 preceded by a methionine; a polypeptide comprising the amino acid sequence of any of SEQ ID NO: 11 -18 with up to 5 single amino acid changes or deletions provided that the polypeptide does not comprise the amino acid sequence of SEQ ID NO: 10.

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.

The present disclosure provides polypeptides that inhibit activity of a CRISPR/Cas effector polypeptide, nucleic acids encoding the polypeptides, and systems comprising the polypeptides and/or nucleic acids encoding the polypeptides. The present disclosure provides methods of inhibiting activity of a CRISRP/Cas effector polypeptide.

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.