Human albumin animal models for drug evaluation, Toxicology and immunogenicity studies

Abstract

An animal model is provided which is genetically engineered to express human serum albumin, and such animals may be advantageously used in assessing drugs, vaccines or other therapeutic compounds that may be used in humans. In addition, an animal model is provided which does not manufacture its own albumin and which has been injected with human serum albumin. Through the use of these animal models, drugs and other chemicals can be more accurately assessed in physiological environments that reflect the conditions to be expected in humans, and such models will be useful in assessing new drugs and evaluating toxic substances for potential dangers as carcinogens, mutagens, etc. Other applications include evaluating immunological properties of various albumin-engineered proteins which might be administered to humans as therapeutics or vaccines, and research of disease states, such as genetic diseases, to provide further insight in treating these diseases.

1 . A transgenic rat whose genome comprises nucleic acid coding for human serum albumin which is expressed in the rat's bloodstream, wherein the gene coding for the native rat serum albumin is replaced by the nucleic acid coding for human serum albumin such that the rat does not express its own natural serum albumin.  
   
   
       2 . The transgenic rat according to  claim 1  wherein the rat has been mutated so that it does not express its own natural serum albumin.  
   
   
       3 . The transgenic rat according to  claim 1  wherein the rat is an NAR rat.  
   
   
       4 . The transgenic rate according to  claim 1  wherein said rat has had its gene for serum albumin knocked out.  
   
   
       5 . A method of testing the efficacy, carcinogenicity, immunogenicity or toxicity of an agent designed to be administered internally to a human selected from the group consisting of vaccines, drugs and other therapeutic compounds comprising the steps of administering internally said agent into the transgenic rat according to  claim 1  and determining the efficacy, carcinogenicity, immunogenicity or toxicity of said agent in said transgenic rat.  
   
   
       6 . The method according to  claim 5  wherein the testing is to evaluate the efficacy of a drug or other therapeutic compound.  
   
   
       7 . The method according to  claim 5  wherein the testing is to evaluate the carcinogenicity or toxigenicity of a drug or other therapeutic compound.  
   
   
       8 . The method according to  claim 5  wherein the testing is to evaluate the immunogenicity or other immunological properties of a vaccine.  
   
   
       9 . A transgenic NAR rat whose genome comprises nucleic acid coding for human serum albumin which is expressed in the animal's bloodstream, wherein the rat does not express its own natural serum albumin.