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Efficacy and immunogenicity of unmodified and pseudouridine-modified mRNA delivered systemically with lipid nanoparticles in vivo

Overview of attention for article published in Biomaterials, December 2016
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (96th percentile)
  • High Attention Score compared to outputs of the same age and source (98th percentile)

Mentioned by

news
1 news outlet
twitter
76 tweeters
patent
40 patents

Citations

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112 Dimensions

Readers on

mendeley
219 Mendeley
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Title
Efficacy and immunogenicity of unmodified and pseudouridine-modified mRNA delivered systemically with lipid nanoparticles in vivo
Published in
Biomaterials, December 2016
DOI 10.1016/j.biomaterials.2016.09.006
Pubmed ID
Authors

Kevin J. Kauffman, Faryal F. Mir, Siddharth Jhunjhunwala, James C. Kaczmarek, Juan E. Hurtado, Jung H. Yang, Matthew J. Webber, Piotr S. Kowalski, Michael W. Heartlein, Frank DeRosa, Daniel G. Anderson

Abstract

mRNA has broad potential for treating diseases requiring protein expression. However, mRNA can also induce an immune response with associated toxicity. Replacement of uridine bases with pseudouridine has been postulated to modulate both mRNA immunogenicity and potency. Here, we explore the immune response and activity of lipid nanoparticle-formulated unmodified and pseudouridine-modified mRNAs administered systemically in vivo. Pseudouridine modification to mRNA had no significant effect on lipid nanoparticle physical properties, protein expression in vivo, or mRNA immunogenicity compared to unmodified mRNA when delivered systemically with liver-targeting lipid nanoparticles, but reduced in vitro transfection levels. Indicators of a transient, extracellular innate immune response to mRNA were observed, including neutrophilia, myeloid cell activation, and up-regulation of four serum cytokines. This study provides insight into the immune responses to mRNA lipid nanoparticles, and suggests that pseudouridine modifications may be unnecessary for therapeutic application of mRNA in the liver.

Twitter Demographics

The data shown below were collected from the profiles of 76 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 219 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Turkey 1 <1%
Unknown 218 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 46 21%
Researcher 32 15%
Student > Bachelor 24 11%
Student > Master 23 11%
Student > Doctoral Student 11 5%
Other 31 14%
Unknown 52 24%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 52 24%
Agricultural and Biological Sciences 29 13%
Pharmacology, Toxicology and Pharmaceutical Science 16 7%
Immunology and Microbiology 14 6%
Engineering 11 5%
Other 39 18%
Unknown 58 26%

Attention Score in Context

This research output has an Altmetric Attention Score of 60. 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 05 January 2023.
All research outputs
#613,961
of 23,053,169 outputs
Outputs from Biomaterials
#128
of 10,321 outputs
Outputs of similar age
#14,062
of 417,555 outputs
Outputs of similar age from Biomaterials
#2
of 131 outputs
Altmetric has tracked 23,053,169 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 10,321 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.7. This one has done particularly well, scoring higher than 98% 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 417,555 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 96% of its contemporaries.
We're also able to compare this research output to 131 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 98% of its contemporaries.