In vivo SELEX for Identification of Brain-penetrating Aptamers
The physiological barriers of the brain impair drug delivery for treatment of many neurological disorders. One delivery approach that has not been investigated for their ability to penetrate the brain is RNA-based aptamers. These molecules can impart delivery to peripheral tissues and circulating im...
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Nature Publishing Group
2013
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564417/ |
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pubmed-35644172013-02-05 In vivo SELEX for Identification of Brain-penetrating Aptamers Cheng, Congsheng Chen, Yong Hong Lennox, Kim A Behlke, Mark A Davidson, Beverly L Original Article The physiological barriers of the brain impair drug delivery for treatment of many neurological disorders. One delivery approach that has not been investigated for their ability to penetrate the brain is RNA-based aptamers. These molecules can impart delivery to peripheral tissues and circulating immune cells, where they act as ligand mimics or can be modified to carry payloads. We developed a library of aptamers and an in vivo evolution protocol to determine whether specific aptamers could be identified that would home to the brain after injection into the peripheral vasculature. Unlike biopanning with recombinant bacteriophage libraries, we found that the aptamer library employed here required more than 15 rounds of in vivo selection for convergence to specific sequences. The aptamer species identified through this approach bound to brain capillary endothelia and penetrated into the parenchyma. The methods described may find general utility for targeting various payloads to the brain. Nature Publishing Group 2013-01 2013-01-08 /pmc/articles/PMC3564417/ /pubmed/23299833 http://dx.doi.org/10.1038/mtna.2012.59 Text en Copyright © 2013 American Society of Gene & Cell Therapy http://creativecommons.org/licenses/by-nc-nd/3.0/ Molecular Therapy-Nucleic Acids is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Cheng, Congsheng Chen, Yong Hong Lennox, Kim A Behlke, Mark A Davidson, Beverly L |
| spellingShingle |
Cheng, Congsheng Chen, Yong Hong Lennox, Kim A Behlke, Mark A Davidson, Beverly L In vivo SELEX for Identification of Brain-penetrating Aptamers |
| author_facet |
Cheng, Congsheng Chen, Yong Hong Lennox, Kim A Behlke, Mark A Davidson, Beverly L |
| author_sort |
Cheng, Congsheng |
| title |
In vivo SELEX for Identification of Brain-penetrating Aptamers |
| title_short |
In vivo SELEX for Identification of Brain-penetrating Aptamers |
| title_full |
In vivo SELEX for Identification of Brain-penetrating Aptamers |
| title_fullStr |
In vivo SELEX for Identification of Brain-penetrating Aptamers |
| title_full_unstemmed |
In vivo SELEX for Identification of Brain-penetrating Aptamers |
| title_sort |
in vivo selex for identification of brain-penetrating aptamers |
| description |
The physiological barriers of the brain impair drug delivery for treatment of many neurological disorders. One delivery approach that has not been investigated for their ability to penetrate the brain is RNA-based aptamers. These molecules can impart delivery to peripheral tissues and circulating immune cells, where they act as ligand mimics or can be modified to carry payloads. We developed a library of aptamers and an in vivo evolution protocol to determine whether specific aptamers could be identified that would home to the brain after injection into the peripheral vasculature. Unlike biopanning with recombinant bacteriophage libraries, we found that the aptamer library employed here required more than 15 rounds of in vivo selection for convergence to specific sequences. The aptamer species identified through this approach bound to brain capillary endothelia and penetrated into the parenchyma. The methods described may find general utility for targeting various payloads to the brain. |
| publisher |
Nature Publishing Group |
| publishDate |
2013 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564417/ |
| _version_ |
1611952590315061248 |