The present invention relates to a microorganism for drug delivery, which has been transformed with a gene construct including a therapeutically active peptide, is delivered safely into the intestines through oral administration, and expresses and secretes a cystatin in the gastrointestinal tract, and also relates to a pharmaceutical composition for prevention or treatment of gastrointestinal disease, which includes the same. The present invention demonstrates the safety and superiority of lactic acid bacteria as a system for delivering a protein-based drug, and thus it is expected the lactic acid bacteria will be widely used as an agent for treatment of gastrointestinal disease in the medical field.

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.

Methods and compositions for treating and/or preventing aging-related conditions are described. The compositions used in the methods include blood plasma and blood plasma fractions derived from blood plasma with efficacy in treating and/or preventing aging-related conditions such as cognitive disorders. The methods relate to a regimen of pulsed dosing of blood plasma or blood plasma fractions.

Methods and compositions for promoting donor-specific tolerance and immunocompetence to a recipient of a solid organ transplant, by implanting an allogeneic solid organ in a recipient in need of a solid organ transplant and further comprising surgical implantation of a tissue-engineered allogeneic cultured postnatal thymus tissue product in the recipient of a solid organ from a donor.

The inventors have unexpectedly discovered that shock and/or potential multi-organ failure due to shock can be effectively treated by administration of liquid high-dose protease inhibitor formulations to a location upstream of where pancreatic proteases are introduced into the gastrointestinal tract. Most preferably, administration is directly to the stomach, for example, via nasogastric tube under a protocol effective to treat shock by such administration without the need of providing significant quantities of the protease inhibitor to the jejunum and/or ileum.

A method for treating a medical condition of a patient with Alpha-2 Macroglobulin (?2M) molecules in an allogeneic or xenogeneic manner, the method includes: drawing whole blood from a donor, separating plasma containing ?2M molecules from other components of the whole blood; isolating the ?2M molecules from the other components of the plasma; and administering at least some of the isolated ?2M molecules to the patient via injection or inhalation, wherein the donor and the patient are different individuals.

Provided are gene therapy technologies, including specifically designed and tested guide RNA sequences for improved base editors, useful for increasing the expression of the gamma-globin gene. The guide RNA sequences may target the BCL11A erythroid enhancer or the gamma-globin promoter, or both at the same time. The base editors can include nucleobase deaminase inhibitor that inhibits the editing activity of the base editors until they are bound to the target sites. These gene therapy technologies are useful for treating diseases including beta-thalassemia and sickle cell anemia, among others.

Methods of preventing and/or treating reperfusion injury are provided. The methods involve administering alpha-2-macroglobulin (A2MG) to a subject with ischemia in one or more tissues or organs, in order to prevent or decrease reperfusion injury when blood flow is restored to the tissues or organs (reperfusion). In some aspects, the patient who is treated has had a heart attack (e.g. acute myocardial infarction, AMI) and the ischemic tissue that is protected from reperfusion injury is heart tissue.

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.

Disclosed is an artificial red blood cell containing purified and enriched hemoglobin that substantially has no enzymatic activity to reduce methemoglobin, transformation of the hemoglobin into methemoglobin. Provided is an artificial red blood cell which comprises: an aqueous solution that contains NADH and/or NADPH and hemoglobin; and a capsule that includes the aqueous solution, wherein the aqueous solution and the capsule substantially have no enzymatic activity to reduce methemoglobin.