PMID- 17892442
OWN - NLM
STAT- MEDLINE
DCOM- 20071217
LR  - 20121115
IS  - 1043-0342 (Print)
IS  - 1043-0342 (Linking)
VI  - 18
IP  - 10
DP  - 2007 Oct
TI  - Development of tissue-targeting hemagglutinating virus of Japan envelope vector 
      for successful delivery of therapeutic gene to mouse skin.
PG  - 881-94
AB  - We report a novel strategy for constructing a tissue-targeting hemagglutinating 
      virus of Japan (HVJ; Sendai virus) envelope vector (HVJ-E), and its application 
      in gene therapy of a mouse model of genetic skin disease. Chimeric genes encoding 
      viral F protein and green fluorescent protein (GFP) were constructed on the basis 
      of various deletion mutants. The product of one chimeric gene, containing signal 
      peptide, transmembrane domain, and the cytoplasmic tail of F protein, was 
      transported to the cell surface and incorporated into new viruses released from 
      HVJ-infected LLC-MK2 cells. For tissue targeting, in the preceding construct GFP 
      was replaced with single-chain antibody (scFv) against mouse desmoglein 3 
      (mDsg3), a desmosomal cadherin found in basal layer keratinocytes of the skin. 
      HVJ encoding scFv-F chimeric protein bound to mDsg3-coated plates much more 
      efficiently than did wild-type HVJ. When chimeric HVJ was injected into a skin 
      blister of a mouse model of epidermolysis bullosa, in which defective expression 
      of type VII collagen results in a failure to secure epidermis to the underlying 
      dermis, viral F protein expression was detected in most of the basal 
      keratinocytes. Furthermore, chimeric HVJ-E introduced type VII collagen 
      expression more efficiently compared with wild-type HVJ in basal keratinocytes of 
      type VII collagen-deficient mouse skin, resulting in efficient amelioration of 
      the genetic defect. Thus, a novel tissue-targeting HVJ-E could be used to 
      successfully target epidermal keratinocytes both in vitro and in vivo.
FAU - Kawachi, Masako
AU  - Kawachi M
AD  - Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, 
      Suita, Osaka 565-0871, Japan.
FAU - Tamai, Katsuto
AU  - Tamai K
FAU - Saga, Kotaro
AU  - Saga K
FAU - Yamazaki, Takehiko
AU  - Yamazaki T
FAU - Fujita, Hiroshi
AU  - Fujita H
FAU - Shimbo, Takashi
AU  - Shimbo T
FAU - Kikuchi, Yasushi
AU  - Kikuchi Y
FAU - Nimura, Keisuke
AU  - Nimura K
FAU - Nishifuji, Koji
AU  - Nishifuji K
FAU - Amagai, Masayuki
AU  - Amagai M
FAU - Uitto, Jouni
AU  - Uitto J
FAU - Kaneda, Yasufumi
AU  - Kaneda Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - 0 (Desmoglein 3)
RN  - 0 (Dsg3 protein, mouse)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Viral Fusion Proteins)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Desmoglein 3/*metabolism
MH  - Epidermolysis Bullosa/genetics/*therapy
MH  - Gene Targeting
MH  - Gene Transfer Techniques
MH  - *Genetic Therapy
MH  - *Genetic Vectors
MH  - Keratinocytes/cytology/*metabolism
MH  - Mice
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Sendai virus/*genetics
MH  - Viral Fusion Proteins/genetics/*metabolism
EDAT- 2007/09/26 09:00
MHDA- 2007/12/18 09:00
CRDT- 2007/09/26 09:00
PHST- 2007/09/26 09:00 [pubmed]
PHST- 2007/12/18 09:00 [medline]
PHST- 2007/09/26 09:00 [entrez]
AID - 10.1089/hum.2007.046 [doi]
PST - ppublish
SO  - Hum Gene Ther. 2007 Oct;18(10):881-94. doi: 10.1089/hum.2007.046.