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Recombinant botulinum neurotoxin A heavy chain-based delivery vehicles for neuronal cell targeting.

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Title: Recombinant botulinum neurotoxin A heavy chain-based delivery vehicles for neuronal cell targeting.
Authors: Ho, Mengfei1,2, Chang, Li-Hsin1, Pires-Alves, Melissa1, Thyagarajan, Baskaran3, Bloom, Jordan E.1, Gu, Zhengrong1, Aberle, Karla K.1, Teymorian, Sasha A.1, Bannai, Yuka1, Johnson, Steven C.1, McArdle, Joseph J.3, Wilson, Brenda A.1,2
Source: PEDS: Protein Engineering, Design & Selection. Mar2011, Vol. 24 Issue 3, p247-253. 7p. 3 Color Photographs, 3 Black and White Photographs.
Subjects: Botulinum toxin, Neurotoxic agents, Antitoxins, Green fluorescent protein, Escherichia coli, Amino acids, Efferent pathways, Laboratory mice
Abstract: The long half-life of botulinum neurotoxin serotype A (BoNT/A) in cells poses a challenge in developing post-exposure therapeutics complementary to existing antitoxin strategies. Delivery vehicles consisting of the toxin heavy chain (HC), including the receptor-binding domain and translocation domain, connected to an inhibitory cargo offer a possible solution for rescuing intoxicated neurons in victims paralyzed from botulism. Here, we report the expression and purification of soluble recombinant prototype green fluorescent protein (GFP) cargo proteins fused to the entire BoNT/A-HC (residues 544–1295) in Escherichia coli with up to a 40 amino acid linker inserted between the cargo and BoNT/A-HC vehicle. We show that these GFP-HC fusion proteins are functionally active and readily taken up by cultured neuronal cells as well as by neuronal cells in mouse motor nerve endings. [ABSTRACT FROM AUTHOR]
Copyright of PEDS: Protein Engineering, Design & Selection is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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  Data: Recombinant botulinum neurotoxin A heavy chain-based delivery vehicles for neuronal cell targeting.
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  Data: <searchLink fieldCode="AR" term="%22Ho%2C+Mengfei%22">Ho, Mengfei</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Chang%2C+Li-Hsin%22">Chang, Li-Hsin</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Pires-Alves%2C+Melissa%22">Pires-Alves, Melissa</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Thyagarajan%2C+Baskaran%22">Thyagarajan, Baskaran</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Bloom%2C+Jordan+E%2E%22">Bloom, Jordan E.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Gu%2C+Zhengrong%22">Gu, Zhengrong</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Aberle%2C+Karla+K%2E%22">Aberle, Karla K.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Teymorian%2C+Sasha+A%2E%22">Teymorian, Sasha A.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Bannai%2C+Yuka%22">Bannai, Yuka</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Johnson%2C+Steven+C%2E%22">Johnson, Steven C.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22McArdle%2C+Joseph+J%2E%22">McArdle, Joseph J.</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Wilson%2C+Brenda+A%2E%22">Wilson, Brenda A.</searchLink><relatesTo>1,2</relatesTo>
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  Data: <searchLink fieldCode="JN" term="%22PEDS%3A+Protein+Engineering%2C+Design+%26+Selection%22">PEDS: Protein Engineering, Design & Selection</searchLink>. Mar2011, Vol. 24 Issue 3, p247-253. 7p. 3 Color Photographs, 3 Black and White Photographs.
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  Data: <searchLink fieldCode="DE" term="%22Botulinum+toxin%22">Botulinum toxin</searchLink><br /><searchLink fieldCode="DE" term="%22Neurotoxic+agents%22">Neurotoxic agents</searchLink><br /><searchLink fieldCode="DE" term="%22Antitoxins%22">Antitoxins</searchLink><br /><searchLink fieldCode="DE" term="%22Green+fluorescent+protein%22">Green fluorescent protein</searchLink><br /><searchLink fieldCode="DE" term="%22Escherichia+coli%22">Escherichia coli</searchLink><br /><searchLink fieldCode="DE" term="%22Amino+acids%22">Amino acids</searchLink><br /><searchLink fieldCode="DE" term="%22Efferent+pathways%22">Efferent pathways</searchLink><br /><searchLink fieldCode="DE" term="%22Laboratory+mice%22">Laboratory mice</searchLink>
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  Label: Abstract
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  Data: The long half-life of botulinum neurotoxin serotype A (BoNT/A) in cells poses a challenge in developing post-exposure therapeutics complementary to existing antitoxin strategies. Delivery vehicles consisting of the toxin heavy chain (HC), including the receptor-binding domain and translocation domain, connected to an inhibitory cargo offer a possible solution for rescuing intoxicated neurons in victims paralyzed from botulism. Here, we report the expression and purification of soluble recombinant prototype green fluorescent protein (GFP) cargo proteins fused to the entire BoNT/A-HC (residues 544–1295) in Escherichia coli with up to a 40 amino acid linker inserted between the cargo and BoNT/A-HC vehicle. We show that these GFP-HC fusion proteins are functionally active and readily taken up by cultured neuronal cells as well as by neuronal cells in mouse motor nerve endings. [ABSTRACT FROM AUTHOR]
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  Label:
  Group: Ab
  Data: <i>Copyright of PEDS: Protein Engineering, Design & Selection is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Text: English
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        PageCount: 7
        StartPage: 247
    Subjects:
      – SubjectFull: Botulinum toxin
        Type: general
      – SubjectFull: Neurotoxic agents
        Type: general
      – SubjectFull: Antitoxins
        Type: general
      – SubjectFull: Green fluorescent protein
        Type: general
      – SubjectFull: Escherichia coli
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      – SubjectFull: Amino acids
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      – SubjectFull: Efferent pathways
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      – SubjectFull: Laboratory mice
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      – TitleFull: Recombinant botulinum neurotoxin A heavy chain-based delivery vehicles for neuronal cell targeting.
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              Text: Mar2011
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              Y: 2011
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