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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Genomic Editing of the HIV-1 Coreceptor CCR5 in Adult Hematopoietic Stem and Progenitor Cells Using Zinc Finger Nucleases
|
|---|---|
| Published in |
Molecular Therapy, April 2013
|
| DOI | 10.1038/mt.2013.65 |
| Pubmed ID | |
| Authors |
Lijing Li, Ludmila Krymskaya, Jianbin Wang, Jill Henley, Anitha Rao, Lan-Feng Cao, Chy-Anh Tran, Monica Torres-Coronado, Agnes Gardner, Nancy Gonzalez, Kenneth Kim, Pei-Qi Liu, Ursula Hofer, Evan Lopez, Philip D Gregory, Qing Liu, Michael C Holmes, Paula M Cannon, John A Zaia, David L DiGiusto |
| Abstract |
The HIV-1 coreceptor CCR5 is a validated target for HIV/AIDS therapy. The apparent elimination of HIV-1 in a patient treated with an allogeneic stem cell transplant homozygous for a naturally occurring CCR5 deletion mutation (CCR5(Δ32/Δ32)) supports the concept that a single dose of HIV-resistant hematopoietic stem cells can provide disease protection. Given the low frequency of naturally occurring CCR5(Δ32/Δ32) donors, we reasoned that engineered autologous CD34(+) hematopoietic stem/progenitor cells (HSPCs) could be used for AIDS therapy. We evaluated disruption of CCR5 gene expression in HSPCs isolated from granulocyte colony-stimulating factor (CSF)-mobilized adult blood using a recombinant adenoviral vector encoding a CCR5-specific pair of zinc finger nucleases (CCR5-ZFN). Our results demonstrate that CCR5-ZFN RNA and protein expression from the adenoviral vector is enhanced by pretreatment of HSPC with protein kinase C (PKC) activators resulting in >25% CCR5 gene disruption and that activation of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway is responsible for this activity. Importantly, using an optimized dose of PKC activator and adenoviral vector we could generate CCR5-modified HSPCs which engraft in a humanized mouse model (albeit at a reduced level) and support multilineage differentiation in vitro and in vivo. Together, these data establish the basis for improved approaches exploiting adenoviral vector delivery in the modification of HSPCs. |
X Demographics
The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 5 | 83% |
| Unknown | 1 | 17% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 83% |
| Scientists | 1 | 17% |
Mendeley readers
The data shown below were compiled from readership statistics for 204 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 5 | 2% |
| Sweden | 1 | <1% |
| Germany | 1 | <1% |
| Spain | 1 | <1% |
| India | 1 | <1% |
| Unknown | 195 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 45 | 22% |
| Researcher | 43 | 21% |
| Student > Bachelor | 32 | 16% |
| Student > Master | 26 | 13% |
| Student > Doctoral Student | 10 | 5% |
| Other | 24 | 12% |
| Unknown | 24 | 12% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 76 | 37% |
| Biochemistry, Genetics and Molecular Biology | 46 | 23% |
| Medicine and Dentistry | 28 | 14% |
| Immunology and Microbiology | 9 | 4% |
| Engineering | 7 | 3% |
| Other | 13 | 6% |
| Unknown | 25 | 12% |
Attention Score in Context
This research output has an Altmetric Attention Score of 14. 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 06 December 2022.
All research outputs
#2,614,811
of 25,374,917 outputs
Outputs from Molecular Therapy
#828
of 4,917 outputs
Outputs of similar age
#20,256
of 194,551 outputs
Outputs of similar age from Molecular Therapy
#8
of 49 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,917 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 13.2. This one has done well, scoring higher than 82% of its peers.
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 194,551 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 89% of its contemporaries.
We're also able to compare this research output to 49 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 83% of its contemporaries.