Linked Life Data

14725787

Source:http://linkedlifedata.com/resource/pubmed/id/14725787

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2004-1-16
pubmed:abstractText
Antibodies or antibody fragments represent a powerful class of targeting moieties to specifically attach proteins to the surface of a given cell or tissue. Since the presence of constant antibody domains in these targeted fusion proteins may have certain disadvantages, we report here the reduction of the targeting epitope to the variable regions of an Ab by the generation of a single chain antibody fragment (scFv). As an effector molecule, we attached the human complement regulatory protein (CRP) decay-accelerating factor (DAF) at its amino-terminus with a scFv specific for TER-119, a red blood cell (RBC) restricted surface antigen of the mouse. This heterologous system enabled us to study (a) the applicability of a scFv as a targeting domain, (b) the functionality of the effector molecule with respect to regulation of the complement cascade in vitro, and (c) the in vivo biodistribution characteristics of a scFv-DAF fusion protein attached to a clinically relevant target cell type. RBCs from C57BL/6 mice loaded in vitro or in vivo with this fusion protein were significantly protected against lysis by human complement. After intravenous injection, a homogeneous population of in vivo tagged RBCs was maintained throughout a 6-day follow-up. This result and in vitro mixing experiments indicated that there was an equilibration of the fusion protein between tagged and non-tagged RBCs. Thus, scFv-mediated targeting of proteins to a selected cell or tissue surface has promise as a means to supplement absent or defective plasma membrane constituents. This approach should therefore be applicable for diseases caused by a membrane protein deficiency such as paroxysmal nocturnal hemoglobinuria (PNH).
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0161-5890
pubmed:author
pubmed:issnType
Print
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
911-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
ScFv-mediated in vivo targeting of DAF to erythrocytes inhibits lysis by complement.
pubmed:affiliation
Division of Rheumatology, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8045, St. Louis, MO 63110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't