Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26046460
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
A minimally invasive, lentiviral based method for the rapid and sustained genetic
manipulation of renal tubules
#MMPMID26046460
Espana-Agusti J
; Tuveson DA
; Adams DJ
; Matakidou A
Sci Rep
2015[Jun]; 5
(?): 11061
PMID26046460
show ga
The accelerated discovery of disease-related genes emerging from genomic studies
has strained the capacity of traditional genetically engineered mouse models
(GEMMs) to provide in-vivo validation. Direct, somatic, genetic engineering
approaches allow for accelerated and flexible genetic manipulation and represent
an attractive alternative to GEMMs. In this study we investigated the
feasibility, safety and efficiency of a minimally invasive, lentiviral based
approach for the sustained in-vivo modification of renal tubular epithelial
cells. Using ultrasound guidance, reporter vectors were directly injected into
the mouse renal parenchyma. We observed transgene expression confined to the
renal cortex (specifically proximal and distal tubules) and sustained beyond 2
months post injection. Furthermore, we demonstrate the ability of this
methodology to induce long-term, in-vivo knockdown of candidate genes either
through somatic recombination of floxed alleles or by direct delivery of specific
shRNA sequences. This study demonstrates that ultrasound-guided injection of
lentiviral vectors provides a safe and efficient method for the genetic
manipulation of renal tubules, representing a quick and versatile alternative to
GEMMs for the functional characterisation of disease-related genes.
free
free
free
