Gene transfer of Hodgkin cell lines via multivalent anti-CD30 scFv displaying bacteriophage.
BACKGROUND
The display of binding ligands, such as recombinant antibody fragments, on the surface of filamentous phage makes it possible to specifically attach these phage particles to target cells. After uptake of the phage, their internal single-stranded DNA is processed by the host cell, which allows transient expression of an encoded eukaryotic gene cassette. This opens the possibility to use bacteriophage as vectors for targeted gene therapy, although the transduction efficiency is very low.


RESULTS
Here we demonstrate the display of an anti-CD30 single chain variable fragment fused to the major coat protein pVIII on the surface of bacteriophage. These phage particles showed an improved binding and transduction efficiency of CD30 positive Hodgkin-lymphoma cells, compared to bacteriophage with the anti-CD30 single chain variable fragment fused to the minor coat protein pIII.


CONCLUSIONS
We can conclude from the results that the postulated multivalency of the anti-CD30-pVIII displaying bacteriophage combined with disseminated display of the anti-CD30 scFv on the whole particle surface is responsible for the improved gene transfer rate. These results mark an important step towards the use of phage particles as a cheap and safe gene transfer vehicle for the gene delivery of the desired target cells via their specific surface receptors.
Chung
Yoon-Suk A
YS
University of Cologne, Institute of Medical Microbiology, Immunology and Hygiene, Goldenfelsstr, 19-21, 50935 Cologne, Germany. alex-y-s-c@gmx.de
Sabel
Katja
K
Krönke
Martin
M
Klimka
Alexander
A
D017104:Bacteriophage M13 / Q000235:genetics* / Q000378:metabolism*; D036022:Capsid Proteins / Q000378:metabolism; D002449:Cell Aggregation; D045744:Cell Line, Tumor; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006689:Hodgkin Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000378:metabolism*; D017730:Ki-1 Antigen / Q000276:immunology*; D019151:Peptide Library; D011485:Protein Binding
D036022:Capsid Proteins; D007135:Immunoglobulin Variable Region; D017730:Ki-1 Antigen; D019151:Peptide Library