hiv tat domain improves cross-correction of human galactocerebrosidase in a gene- and flanking sequence-dependent manner
Clicks: 12
ID: 255583
2013
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This
article has not been analysed, so there is no overall score —
reader engagement is measured and shown alongside.
Reader Engagement
Popular Article
3.3
/100
12 views
1 readers
AI Quality Assessment
Not analyzed
Readership in this journal
PopularRanked #76 of 77 articles by views in coordination chemistry reviews
Most read
Least read
Bar heights use a square-root scale.
Mint this article as an NFT
Not yet mintedCreate a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.
5
SUSD
one-off · no wallet required
Abstract
Krabbe disease is a devastating neurodegenerative lysosomal storage disorder caused by a deficiency of β-galactocerebrosidase (GALC). Gene therapy is a promising therapeutic approach for Krabbe disease. As the human brain is large and it is difficult to achieve global gene transduction, the efficacy of cross-correction is a critical determinant of the outcome of gene therapy for this disease. We investigated whether HIV Tat protein transduction domain (PTD) can improve the cross-correction of GALC. Tat-PTD significantly increased (~6-fold) cross-correction of GALC through enhanced secretion and uptake in a cell-culture model system. The effects of Tat-PTD were gene and flanking amino acids dependent. Tat-fusion increased the secretion of α-galactosidase A (α-gal A), but this did not improve its cross-correction. Tat-fusion did not change either secretion or uptake of β-glucocerebrosidase (GC). Tat-PTD increased GALC protein synthesis, abolished reactivity of GC to the 8E4 antibody, and likely reduced mannose phosphorylation in all these lysosomal enzymes. This study demonstrated that Tat-PTD can be useful for increasing cross-correction efficiency of lysosomal enzymes. However, Tat-PTD is not a mere adhesive motif but possesses a variety of biological functions. Therefore, the potential beneficial effect of Tat-PTD should be assessed individually on each lysosomal enzyme.
| Reference Key |
meng2013molecularhiv
Use this key to autocite in the manuscript while using
SciMatic Manuscript Manager or Thesis Manager
|
|---|---|
| Authors | ;Xing-Li Meng;Yoshikatsu Eto;Raphael Schiffmann;Jin-Song Shen |
| Journal | coordination chemistry reviews |
| Year | 2013 |
| DOI |
10.1038/mtna.2013.57
|
| URL | |
| Keywords |
Citations
No citations found. To add a citation, contact the admin at info@scimatic.org
Comments
No comments yet. Be the first to comment on this article.