The potential efficacy of gene delivery is dictated by the infectivity profile of existing vectors, which is often restrictive. In order to target cells and organs for which no efficient vector is currently available, a promising approach would be to engineer vectors with novel transduction profiles. Applications that involve injecting adenovirus (Ad) vectors into the bloodstream require that native tropism for the liver be removed, and that targeting moieties be engineered into the capsid. We previously reported that pseudotyping the Ad serotype 5 fiber for that of Ad19p results in reduced hepatic transduction. In this study we show that this may be caused, at least in part, by a reduction in the capacity of the Ad19p-based virus to bind blood coagulation factors. It is therefore a potential candidate for vector retargeting, focusing on the kidney as a therapeutic target. We used in vivo phage display in rats, and identified peptides HTTHREP and HITSLLS that homed to the kidneys following intravenous injection. We engineered the HI loop of Ad19p to accommodate peptide insertions and clones. Intravenous delivery of each peptide-modified virus resulted in selective renal targeting, with HTTHREP and HITSLLS-targeted viruses selectively transducing tubular epithelium and glomeruli, respectively. Our study has important implications for the use of genetic engineering of Ad fibers to produce targeted gene delivery vectors.
Pharmacology, Toxicology and Pharmaceutical Science
3
7%
Medicine and Dentistry
3
7%
Business, Management and Accounting
2
4%
Other
3
7%
Unknown
14
31%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 September 2019.
All research outputs
#7,432,872
of 34,054,827 outputs
Outputs from Molecular Therapy
#3,006
of 6,835 outputs
Outputs of similar age
#26,499
of 120,215 outputs
Outputs of similar age from Molecular Therapy
#26
of 73 outputs
Altmetric has tracked 34,054,827 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 6,835 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 13.2. This one is in the 46th percentile – i.e., 46% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 120,215 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 65% of its contemporaries.
We're also able to compare this research output to 73 others from the same source and published within six weeks on either side of this one. This one is in the 47th percentile – i.e., 47% of its contemporaries scored the same or lower than it.
