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...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2013-01-01
|
Series: | Molecular Therapy: Nucleic Acids |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253116301275 |
id |
doaj-515162b715bf44448c52b7188409d4e5 |
---|---|
record_format |
Article |
spelling |
doaj-515162b715bf44448c52b7188409d4e52020-11-24T21:43:16ZengElsevierMolecular Therapy: Nucleic Acids2162-25312013-01-012C10.1038/mtna.2012.59In vivo SELEX for Identification of Brain-penetrating AptamersCongsheng Cheng0Yong Hong Chen1Kim A Lennox2Mark A Behlke3Beverly L Davidson4Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USADepartment of Internal Medicine, University of Iowa, Iowa City, Iowa, USAIntegrated DNA Technologies, Inc., Coralville, Iowa, USAIntegrated DNA Technologies, Inc., Coralville, Iowa, USADepartment of Internal Medicine, University of Iowa, Iowa City, Iowa, USAThe 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.http://www.sciencedirect.com/science/article/pii/S2162253116301275blood–brain barrierin vivo selectionmouseRNA |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Congsheng Cheng Yong Hong Chen Kim A Lennox Mark A Behlke Beverly L Davidson |
spellingShingle |
Congsheng Cheng Yong Hong Chen Kim A Lennox Mark A Behlke Beverly L Davidson In vivo SELEX for Identification of Brain-penetrating Aptamers Molecular Therapy: Nucleic Acids blood–brain barrier in vivo selection mouse RNA |
author_facet |
Congsheng Cheng Yong Hong Chen Kim A Lennox Mark A Behlke Beverly L Davidson |
author_sort |
Congsheng Cheng |
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 |
publisher |
Elsevier |
series |
Molecular Therapy: Nucleic Acids |
issn |
2162-2531 |
publishDate |
2013-01-01 |
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. |
topic |
blood–brain barrier in vivo selection mouse RNA |
url |
http://www.sciencedirect.com/science/article/pii/S2162253116301275 |
work_keys_str_mv |
AT congshengcheng invivoselexforidentificationofbrainpenetratingaptamers AT yonghongchen invivoselexforidentificationofbrainpenetratingaptamers AT kimalennox invivoselexforidentificationofbrainpenetratingaptamers AT markabehlke invivoselexforidentificationofbrainpenetratingaptamers AT beverlyldavidson invivoselexforidentificationofbrainpenetratingaptamers |
_version_ |
1725914498589523968 |