Design of Yeast-Secreted Albumin Derivatives for Human Therapy: Biological and Antiviral Properties of a Serum Albumin-CD4 Genetic Conjugate
Due to its remarkably long half-life, together with its wide in vivo distribution and its lack of enzymatic or immunological functions, human serum albumin (HSA) represents an optimal carrier for therapeutic peptides/proteins aimed at interacting with cellular or molecular components of the vascular...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1992-03, Vol.89 (5), p.1904-1908 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Yeh, Patrice Landais, Didier Lemaitre, Marc Maury, Isabelle Crenne, Jean-Yves Becquart, Jerome Murry-Brelier, Anne Boucher, Francoise Montay, Guy Fleer, Reinhard Hirel, Philippe-Herve Mayaux, Jean-Francois Klatzmann, David |
| description | Due to its remarkably long half-life, together with its wide in vivo distribution and its lack of enzymatic or immunological functions, human serum albumin (HSA) represents an optimal carrier for therapeutic peptides/proteins aimed at interacting with cellular or molecular components of the vascular and interstitial compartments. As an example, we designed a genetically engineered HSA-CD4 hybrid aimed at specifically blocking the entry of the human immunodeficiency virus into CD4+cells. In contrast with CD4, HSA-CD4 is correctly processed and efficiently secreted by Kluyveromyces yeasts. In addition, its CD4 moiety exhibits binding and antiviral in vitro properties similar to those of soluble CD4. Finally, the elimination half-life of HSA-CD4 in a rabbit experimental model is comparable to that of control HSA and 140-fold higher than that of soluble CD4. These results indicate that the genetic fusion of bioactive peptides to HSA is a plausible approach toward the design and recovery of secreted therapeutic HSA derivatives with appropriate pharmacokinetic properties. |
| doi_str_mv | 10.1073/pnas.89.5.1904 |
| format | Article |
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As an example, we designed a genetically engineered HSA-CD4 hybrid aimed at specifically blocking the entry of the human immunodeficiency virus into CD4+cells. In contrast with CD4, HSA-CD4 is correctly processed and efficiently secreted by Kluyveromyces yeasts. In addition, its CD4 moiety exhibits binding and antiviral in vitro properties similar to those of soluble CD4. Finally, the elimination half-life of HSA-CD4 in a rabbit experimental model is comparable to that of control HSA and 140-fold higher than that of soluble CD4. These results indicate that the genetic fusion of bioactive peptides to HSA is a plausible approach toward the design and recovery of secreted therapeutic HSA derivatives with appropriate pharmacokinetic properties.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.89.5.1904</identifier><identifier>PMID: 1542690</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>Acquired immune deficiency syndrome ; AIDS ; AIDS/HIV ; albumin ; Animals ; Antibodies, Monoclonal - immunology ; antiviral activity ; Antiviral drugs ; Antivirals ; Base Sequence ; Binding, Competitive ; Biological and medical sciences ; Biotechnology ; CD4 antigen ; CD4 Antigens - chemistry ; CD4 Antigens - metabolism ; Cell lines ; Fundamental and applied biological sciences. Psychology ; Genetic Vectors ; Half lives ; Health savings accounts ; Health. Pharmaceutical industry ; HIV ; HIV - growth & development ; HIV - metabolism ; Human genetics ; Industrial applications and implications. Economical aspects ; Kluyveromyces ; Kluyveromyces - genetics ; Molecular Sequence Data ; Oligodeoxyribonucleotides - chemistry ; Production of active biomolecules ; Proteins ; Rabbits ; Receptors, Virus - chemistry ; Receptors, Virus - metabolism ; Recombinant Fusion Proteins - pharmacokinetics ; Serum Albumin - chemistry ; Serum Albumin - pharmacokinetics ; Solubility ; Virus Replication ; Yeasts</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1992-03, Vol.89 (5), p.1904-1908</ispartof><rights>Copyright 1992 The National Academy of Sciences of the United States of America</rights><rights>1992 INIST-CNRS</rights><rights>Copyright National Academy of Sciences Mar 1, 1992</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c646t-e840caa4e6604922b2472120a517187cd9726a693e6b152d1b94368316d13a073</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/89/5.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2358898$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2358898$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27922,27923,53789,53791,58015,58248</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5133035$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1542690$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yeh, Patrice</creatorcontrib><creatorcontrib>Landais, Didier</creatorcontrib><creatorcontrib>Lemaitre, Marc</creatorcontrib><creatorcontrib>Maury, Isabelle</creatorcontrib><creatorcontrib>Crenne, Jean-Yves</creatorcontrib><creatorcontrib>Becquart, Jerome</creatorcontrib><creatorcontrib>Murry-Brelier, Anne</creatorcontrib><creatorcontrib>Boucher, Francoise</creatorcontrib><creatorcontrib>Montay, Guy</creatorcontrib><creatorcontrib>Fleer, Reinhard</creatorcontrib><creatorcontrib>Hirel, Philippe-Herve</creatorcontrib><creatorcontrib>Mayaux, Jean-Francois</creatorcontrib><creatorcontrib>Klatzmann, David</creatorcontrib><title>Design of Yeast-Secreted Albumin Derivatives for Human Therapy: Biological and Antiviral Properties of a Serum Albumin-CD4 Genetic Conjugate</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Due to its remarkably long half-life, together with its wide in vivo distribution and its lack of enzymatic or immunological functions, human serum albumin (HSA) represents an optimal carrier for therapeutic peptides/proteins aimed at interacting with cellular or molecular components of the vascular and interstitial compartments. As an example, we designed a genetically engineered HSA-CD4 hybrid aimed at specifically blocking the entry of the human immunodeficiency virus into CD4+cells. In contrast with CD4, HSA-CD4 is correctly processed and efficiently secreted by Kluyveromyces yeasts. In addition, its CD4 moiety exhibits binding and antiviral in vitro properties similar to those of soluble CD4. Finally, the elimination half-life of HSA-CD4 in a rabbit experimental model is comparable to that of control HSA and 140-fold higher than that of soluble CD4. These results indicate that the genetic fusion of bioactive peptides to HSA is a plausible approach toward the design and recovery of secreted therapeutic HSA derivatives with appropriate pharmacokinetic properties.</description><subject>Acquired immune deficiency syndrome</subject><subject>AIDS</subject><subject>AIDS/HIV</subject><subject>albumin</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>antiviral activity</subject><subject>Antiviral drugs</subject><subject>Antivirals</subject><subject>Base Sequence</subject><subject>Binding, Competitive</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>CD4 antigen</subject><subject>CD4 Antigens - chemistry</subject><subject>CD4 Antigens - metabolism</subject><subject>Cell lines</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetic Vectors</subject><subject>Half lives</subject><subject>Health savings accounts</subject><subject>Health. Pharmaceutical industry</subject><subject>HIV</subject><subject>HIV - growth & development</subject><subject>HIV - metabolism</subject><subject>Human genetics</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Kluyveromyces</subject><subject>Kluyveromyces - genetics</subject><subject>Molecular Sequence Data</subject><subject>Oligodeoxyribonucleotides - chemistry</subject><subject>Production of active biomolecules</subject><subject>Proteins</subject><subject>Rabbits</subject><subject>Receptors, Virus - chemistry</subject><subject>Receptors, Virus - metabolism</subject><subject>Recombinant Fusion Proteins - pharmacokinetics</subject><subject>Serum Albumin - chemistry</subject><subject>Serum Albumin - pharmacokinetics</subject><subject>Solubility</subject><subject>Virus Replication</subject><subject>Yeasts</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkkFvEzEQhVcIVELhygkkC6HeNthe22sjLiWBFqkSSC0HTpazmU0d7drB9kb0P_Cj8SppCBzgZFnve8_jmSmK5wRPCa6rNxtn4lSqKZ8ShdmDYkKwIqVgCj8sJhjTupSMssfFkxjXGGPFJT4pTghnVCg8KX7OIdqVQ75F38DEVF5DEyDBEp13i6G3Ds0h2K1JdgsRtT6gy6E3Dt3cQjCbu7fovfWdX9nGdMi47HKZtCHfvgS_gZBstuVwg64hDP19ajmbM3QBDpJt0My79bAyCZ4Wj1rTRXi2P0-Lrx8_3Mwuy6vPF59m51dlI5hIJUiGG2MYCIGZonRBWU0JxYaTmsi6WaqaCiNUBWJBOF2ShWKVkBURS1KZ3LTT4t0udzMselg24FKuWG-C7U24095Y_afi7K1e-a1mkgua7Wd7e_DfB4hJ9zY20HXGgR-irqmscinqvyARhHLKx4Je_QWu_RBc7oGmmNCa1WSEpjuoCT7GAO2hYIL1uAt63AUtleZ63IVseHn8zd_4bvhZf73XTczza4NxjY0HjJOqwhU_ihnj79XjZ87-pet26LoEP1IGX-zAdUw-HEhacSmVrH4BXljdfA</recordid><startdate>19920301</startdate><enddate>19920301</enddate><creator>Yeh, Patrice</creator><creator>Landais, Didier</creator><creator>Lemaitre, Marc</creator><creator>Maury, Isabelle</creator><creator>Crenne, Jean-Yves</creator><creator>Becquart, Jerome</creator><creator>Murry-Brelier, Anne</creator><creator>Boucher, Francoise</creator><creator>Montay, Guy</creator><creator>Fleer, Reinhard</creator><creator>Hirel, Philippe-Herve</creator><creator>Mayaux, Jean-Francois</creator><creator>Klatzmann, David</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7QO</scope><scope>M81</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19920301</creationdate><title>Design of Yeast-Secreted Albumin Derivatives for Human Therapy: Biological and Antiviral Properties of a Serum Albumin-CD4 Genetic Conjugate</title><author>Yeh, Patrice ; Landais, Didier ; Lemaitre, Marc ; Maury, Isabelle ; Crenne, Jean-Yves ; Becquart, Jerome ; Murry-Brelier, Anne ; Boucher, Francoise ; Montay, Guy ; Fleer, Reinhard ; Hirel, Philippe-Herve ; Mayaux, Jean-Francois ; Klatzmann, David</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c646t-e840caa4e6604922b2472120a517187cd9726a693e6b152d1b94368316d13a073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Acquired immune deficiency syndrome</topic><topic>AIDS</topic><topic>AIDS/HIV</topic><topic>albumin</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>antiviral activity</topic><topic>Antiviral drugs</topic><topic>Antivirals</topic><topic>Base Sequence</topic><topic>Binding, Competitive</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>CD4 antigen</topic><topic>CD4 Antigens - chemistry</topic><topic>CD4 Antigens - metabolism</topic><topic>Cell lines</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetic Vectors</topic><topic>Half lives</topic><topic>Health savings accounts</topic><topic>Health. Pharmaceutical industry</topic><topic>HIV</topic><topic>HIV - growth & development</topic><topic>HIV - metabolism</topic><topic>Human genetics</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Kluyveromyces</topic><topic>Kluyveromyces - genetics</topic><topic>Molecular Sequence Data</topic><topic>Oligodeoxyribonucleotides - chemistry</topic><topic>Production of active biomolecules</topic><topic>Proteins</topic><topic>Rabbits</topic><topic>Receptors, Virus - chemistry</topic><topic>Receptors, Virus - metabolism</topic><topic>Recombinant Fusion Proteins - pharmacokinetics</topic><topic>Serum Albumin - chemistry</topic><topic>Serum Albumin - pharmacokinetics</topic><topic>Solubility</topic><topic>Virus Replication</topic><topic>Yeasts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yeh, Patrice</creatorcontrib><creatorcontrib>Landais, Didier</creatorcontrib><creatorcontrib>Lemaitre, Marc</creatorcontrib><creatorcontrib>Maury, Isabelle</creatorcontrib><creatorcontrib>Crenne, Jean-Yves</creatorcontrib><creatorcontrib>Becquart, Jerome</creatorcontrib><creatorcontrib>Murry-Brelier, Anne</creatorcontrib><creatorcontrib>Boucher, Francoise</creatorcontrib><creatorcontrib>Montay, Guy</creatorcontrib><creatorcontrib>Fleer, Reinhard</creatorcontrib><creatorcontrib>Hirel, Philippe-Herve</creatorcontrib><creatorcontrib>Mayaux, Jean-Francois</creatorcontrib><creatorcontrib>Klatzmann, David</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Biochemistry Abstracts 3</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yeh, Patrice</au><au>Landais, Didier</au><au>Lemaitre, Marc</au><au>Maury, Isabelle</au><au>Crenne, Jean-Yves</au><au>Becquart, Jerome</au><au>Murry-Brelier, Anne</au><au>Boucher, Francoise</au><au>Montay, Guy</au><au>Fleer, Reinhard</au><au>Hirel, Philippe-Herve</au><au>Mayaux, Jean-Francois</au><au>Klatzmann, David</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design of Yeast-Secreted Albumin Derivatives for Human Therapy: Biological and Antiviral Properties of a Serum Albumin-CD4 Genetic Conjugate</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1992-03-01</date><risdate>1992</risdate><volume>89</volume><issue>5</issue><spage>1904</spage><epage>1908</epage><pages>1904-1908</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>Due to its remarkably long half-life, together with its wide in vivo distribution and its lack of enzymatic or immunological functions, human serum albumin (HSA) represents an optimal carrier for therapeutic peptides/proteins aimed at interacting with cellular or molecular components of the vascular and interstitial compartments. As an example, we designed a genetically engineered HSA-CD4 hybrid aimed at specifically blocking the entry of the human immunodeficiency virus into CD4+cells. In contrast with CD4, HSA-CD4 is correctly processed and efficiently secreted by Kluyveromyces yeasts. In addition, its CD4 moiety exhibits binding and antiviral in vitro properties similar to those of soluble CD4. Finally, the elimination half-life of HSA-CD4 in a rabbit experimental model is comparable to that of control HSA and 140-fold higher than that of soluble CD4. These results indicate that the genetic fusion of bioactive peptides to HSA is a plausible approach toward the design and recovery of secreted therapeutic HSA derivatives with appropriate pharmacokinetic properties.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>1542690</pmid><doi>10.1073/pnas.89.5.1904</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1992-03, Vol.89 (5), p.1904-1908 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_pascalfrancis_primary_5133035 |
| source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Acquired immune deficiency syndrome AIDS AIDS/HIV albumin Animals Antibodies, Monoclonal - immunology antiviral activity Antiviral drugs Antivirals Base Sequence Binding, Competitive Biological and medical sciences Biotechnology CD4 antigen CD4 Antigens - chemistry CD4 Antigens - metabolism Cell lines Fundamental and applied biological sciences. Psychology Genetic Vectors Half lives Health savings accounts Health. Pharmaceutical industry HIV HIV - growth & development HIV - metabolism Human genetics Industrial applications and implications. Economical aspects Kluyveromyces Kluyveromyces - genetics Molecular Sequence Data Oligodeoxyribonucleotides - chemistry Production of active biomolecules Proteins Rabbits Receptors, Virus - chemistry Receptors, Virus - metabolism Recombinant Fusion Proteins - pharmacokinetics Serum Albumin - chemistry Serum Albumin - pharmacokinetics Solubility Virus Replication Yeasts |
| title | Design of Yeast-Secreted Albumin Derivatives for Human Therapy: Biological and Antiviral Properties of a Serum Albumin-CD4 Genetic Conjugate |
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