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A Novel Class of An...
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Chang, Chien-HsingMorris Plains, New Jersey, United States of America
(författare)
A Novel Class of Anti-HIV Agents with Multiple Copies of Enfuvirtide Enhances Inhibition of Viral Replication and Cellular Transmission In Vitro
- Artikel/kapitelEngelska2012
Förlag, utgivningsår, omfång ...
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2012-07-23
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Public Library of Science (PLoS),2012
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:liu-80201
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-80201URI
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https://doi.org/10.1371/journal.pone.0041235DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:125066740URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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We constructed novel HIV-1 fusion inhibitors that may overcome the current limitations of enfuvirtide, the first such therapeutic in this class. The three prototypes generated by the Dock-and-Lock (DNL) technology to comprise four copies of enfuvirtide tethered site-specifically to the Fc end of different humanized monoclonal antibodies potently neutralize primary isolates (both R5-tropic and X4-tropic), as well as T-cell-adapted strains of HIV-1 in vitro. All three prototypes show EC50 values in the subnanomolar range, which are 10- to 100-fold lower than enfuvirtide and attainable whether or not the constitutive antibody targets HIV-1. The potential of such conjugates to purge latently infected cells was also demonstrated in a cell-to-cell viral inhibition assay by measuring their efficacy to inhibit the spread of HIV-1LAI from infected human peripheral blood mononuclear cells to Jurkat T cells over a period of 30 days following viral activation with 100 nM SAHA (suberoylanilide hydroxamic acid). The IgG-like half-life was not significantly different from that of the parental antibody, as shown by the mean serum concentration of one prototype in mice at 72 h. These encouraging results provide a rationale to develop further novel anti-HIV agents by coupling additional antibodies of interest with alternative HIV-inhibitors via recombinantly-produced, self-assembling, modules.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Hinkula, JormaLinköpings universitet,Molekylär virologi,Hälsouniversitetet(Swepub:liu)jorhi40
(författare)
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Loo, MeiyuMorris Plains, New Jersey, United States of America
(författare)
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Falkeborn, TinaLinköpings universitet,Molekylär virologi,Hälsouniversitetet(Swepub:liu)tinlu81
(författare)
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Li, RongxiuMorris Plains, New Jersey, United States of America
(författare)
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Cardillo, Thomas M.Morris Plains, New Jersey, United States of America
(författare)
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Rossi, Edmund A.Morris Plains, New Jersey, United States of America
(författare)
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Goldenberg, David M.Morris Plains, New Jersey, United States of America
(författare)
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Wahren, BrittaKarolinska Institutet,Karolinska Institutet, Stockholm, Sweden
(författare)
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Morris Plains, New Jersey, United States of AmericaMolekylär virologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:PLOS ONE: Public Library of Science (PLoS)7:7, s. e41235-e412351932-6203
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