The HIV Tat protein transduction domain improves the biodistribution of β-glucuronidase expressed from recombinant viral vectors

Haibin Xia, Qinwen Mao, Beverly L. Davidson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

150 Scopus citations

Abstract

Treatment of inherited genetic diseases of the brain remains an intractable problem. Methods to improve the distribution of enzymes that are injected or expressed from transduced cells will be required for many human brain therapies. Recent studies showed that a peptide, the protein transduction domain (PTD) from HIV Tat, could improve the distribution of cytoplasmic reporter proteins when administered systemically as fusion proteins or cross-linked chimeras. The utility of this motif for noncytoplasmic proteins has not been determined. Here, we tested how the Tat motif affected uptake and biodistribution of the lysosomal enzyme β-glucuronidase, the protein deficient in the disease mucopolysaccharidosis VII, when expressed from viral vectors. The Tat motif allowed for mannose-6-phosphate (M6P) independent uptake in vitro and significantly increased the distribution of β-glucuronidase secreted from transduced cells after intravenous or direct brain injection in mice of recombinant vectors. Thus, enzymes modified to contain protein transduction motifs may represent a general strategy for improving the distribution of secreted proteins following in vivo gene transfer.

Original languageEnglish (US)
Pages (from-to)640-644
Number of pages5
JournalNature biotechnology
Volume19
Issue number7
DOIs
StatePublished - Jul 20 2001

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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