Enhanced delivery efficiency of recombinant adenovirus into tumor and mesenchymal stem cells by a novel PTD.
Protein transduction domains (PTDs) are small peptides that facilitate the transduction of large molecules such as polyproteins, DNA and viruses into a eukaryotic cell. Here, we demonstrated that a novel PTD (HP4) derived from herring protamine appeared to enter C6Bu1 rat glioma cell lines more rapidly than other known PTDs such as Tat, Antp and Hph-1. Moreover, HP4 significantly enhanced in vitro transduction of recombinant adenoviruses (rAds) into various cancer cell lines, mesenchymal stem cells (MSCs) and dendritic cells, which are relatively resistant to rAd infection. Enhancement of rAd delivery into C6Bu1 and MSCs by HP4 is 20 and 7 times higher than that by Tat, respectively. The increase in the expression of rAd encoding IL-12N220L by HP4 is proportional to its antitumor effect in the ex vivo transduced mouse colon cancer model. Thus, these results suggest that HP4 could be utilized to improve the transduction efficiency of rAd, resulting in enhanced efficacy of rAd-mediated gene therapy, especially for ex vivo-transduced cell therapy.
Youn
J-I
JI
1Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea.
Park
S-H
SH
Jin
H-T
HT
Lee
C-G
CG
Seo
S-H
SH
Song
M-Y
MY
Lee
C-W
CW
Sung
Y-C
YC
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy* / Q000821:virology; D050130:Oncolytic Virotherapy / Q000379:methods*; D011479:Protamines / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics*; D051381:Rats; D014161:Transduction, Genetic / Q000379:methods*
D011479:Protamines; D018664:Interleukin-12