Generation of hemoglobin-based oxygen carriers using elastin-like polypeptides

Abstract

Described herein is the use of elastin-like polypeptides to generate hemoglobin-based oxygen carriers as a means of preventing and treating conditions caused by blood loss or anemia, for example, hemorrhagic shock. Elastin-like polypeptides are capable of creating therapeutically functional fusion proteins through genetic engineering with a therapeutic agent, for example, hemoglobin and biologic equivalent thereof. Specific forms of these fusion proteins have the ability to form into spherical nanoparticles possessing a therapeutically agent at their core. This provides a unique basis for employing elastin-like polypeptides as hemoglobin carriers in the manufacture of blood substitutes.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of priority to U.S. Provisional Application No. 62 / 089,885, filed Dec. 10, 2014, entitled “GENERATION OF HEMOGLOBIN-BASED OXYGEN CARRIERS USING ELASTIN-LIKE POLYPEPTIDES”, the content of which is incorporated by reference herein in its entirety.FIELD OF INVENTION[0002]The present invention relates generally to artificial or synthetic blood substitutes.BACKGROUND OF THE INVENTION[0003]The Circulatory System and the Nature of Hemoglobin[0004]Blood, the means for delivering oxygen (O2) and nutrients to the tissues and removing carbon dioxide (CO2) and waste products from the tissues for excretion, is composed of plasma in which red blood cells (RBCs or erythrocytes), white blood cells (WBCs), and platelets are suspended. The functions of blood can be grouped generally as maintenance of intravascular volume, delivery of oxygen to tissues, provision of coagulation factors, provision of some defense mechanism...

AI Technical Summary

Benefits of technology

[0054]According to one aspect, the described invention provides a biocompatible pharmaceutical composition comprising a therapeutic amount of a complex comprising a polymer in association with a hemoglobin (Hb), a Hb subunit(s), a Hb fragment(s), a Hb derivative(s), or a functional equivalent thereof that stores and releases oxygen in accordan

Problems solved by technology

It is reported that over 40% of all trauma-related deaths within the first 24 hours results from hemorrhagic shock, which can be rapidly fatal; serious car accidents, battlefield injuries, and complications during child delivery are other examples of incidents leading to hemorrhagic shock.

The overwhelming cause of mortality in each of these cases is a loss of oxygen-carrying blood.

However, blood transfusion is not readily done before reaching a hospital facility due to disadvantages and constraints of blood transfusion that are discussed below.

First, due to the irregular nature of blood donations, blood supply shortages are common.

Second, there may be a shortage of a patient's blood type.

Third, transfused blood may be contaminated with infectious agents.

Fourth, donated blood has a short stored shelf life (42 days) and must be stored in a refrigerated environment.

Stored blood also loses 2,3-diphosphoglycerate (2,3-DPG) as time progresses, increasing its oxygen affinity and impairing oxygen unloading capacity in tissues.

Fifth, complications can occur with blood transfusion due to inaccurate cross-matching, which remains the leading direct cause of death resulting from blood transfusion.

Sixth, the greatest risk of transfusion may be the alterations it induces in recipients' immunological function.

Multiple blood transfusions may eventually lead to a severe systemic inflammatory response,

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