BRAIDing receptors for cell-specific targeting
Systemic toxicity is a major challenge in the development of therapeutics. Consequently, cell-type-specific targeting is needed to improve on-target efficacy while reducing off-target toxicity. Here, we describe a cell-targeting system we have termed BRAID (BRidged Activation by Intra/intermolecular...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2024-01-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/90221 |
| _version_ | 1797360567259758592 |
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| author | Hui Chen Sung-Jin Lee Ryan Li Asmiti Sura Nicholas Suen Archana Dilip Yan Pomogov Meghah Vuppalapaty Timothy T Suen Chenggang Lu Yorick Post Yang Li |
| author_facet | Hui Chen Sung-Jin Lee Ryan Li Asmiti Sura Nicholas Suen Archana Dilip Yan Pomogov Meghah Vuppalapaty Timothy T Suen Chenggang Lu Yorick Post Yang Li |
| author_sort | Hui Chen |
| collection | DOAJ |
| description | Systemic toxicity is a major challenge in the development of therapeutics. Consequently, cell-type-specific targeting is needed to improve on-target efficacy while reducing off-target toxicity. Here, we describe a cell-targeting system we have termed BRAID (BRidged Activation by Intra/intermolecular Division) whereby an active molecule is divided into two inactive or less active parts that are subsequently brought together via a so-called ‘bridging receptor’ on the target cell. This concept was validated using the WNT/β-catenin signaling system, demonstrating that a multivalent WNT agonist molecule divided into two inactive components assembled from different epitopes via the hepatocyte receptor βKlotho induces signaling specifically on hepatocytes. These data provide proof of concept for this cell-specific targeting strategy, and in principle, this may also allow activation of multiple signaling pathways where desirable. This approach has broad application potential for other receptor systems. |
| first_indexed | 2024-03-08T15:41:37Z |
| format | Article |
| id | doaj.art-b18a4fedb9594fe39bd8ab03b0fe2af9 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-08T15:41:37Z |
| publishDate | 2024-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-b18a4fedb9594fe39bd8ab03b0fe2af92024-01-09T15:00:24ZengeLife Sciences Publications LtdeLife2050-084X2024-01-011210.7554/eLife.90221BRAIDing receptors for cell-specific targetingHui Chen0Sung-Jin Lee1Ryan Li2Asmiti Sura3Nicholas Suen4Archana Dilip5Yan Pomogov6Meghah Vuppalapaty7Timothy T Suen8Chenggang Lu9Yorick Post10Yang Li11https://orcid.org/0000-0002-7134-5685Surrozen Inc, South San Francisco, United StatesSurrozen Inc, South San Francisco, United StatesSurrozen Inc, South San Francisco, United StatesSurrozen Inc, South San Francisco, United StatesSurrozen Inc, South San Francisco, United StatesSurrozen Inc, South San Francisco, United StatesSurrozen Inc, South San Francisco, United StatesSurrozen Inc, South San Francisco, United StatesSurrozen Inc, South San Francisco, United StatesSurrozen Inc, South San Francisco, United StatesSurrozen Inc, South San Francisco, United StatesSurrozen Inc, South San Francisco, United StatesSystemic toxicity is a major challenge in the development of therapeutics. Consequently, cell-type-specific targeting is needed to improve on-target efficacy while reducing off-target toxicity. Here, we describe a cell-targeting system we have termed BRAID (BRidged Activation by Intra/intermolecular Division) whereby an active molecule is divided into two inactive or less active parts that are subsequently brought together via a so-called ‘bridging receptor’ on the target cell. This concept was validated using the WNT/β-catenin signaling system, demonstrating that a multivalent WNT agonist molecule divided into two inactive components assembled from different epitopes via the hepatocyte receptor βKlotho induces signaling specifically on hepatocytes. These data provide proof of concept for this cell-specific targeting strategy, and in principle, this may also allow activation of multiple signaling pathways where desirable. This approach has broad application potential for other receptor systems.https://elifesciences.org/articles/90221cell targetingWNTstem cellfrizzledLRPinduced proximity |
| spellingShingle | Hui Chen Sung-Jin Lee Ryan Li Asmiti Sura Nicholas Suen Archana Dilip Yan Pomogov Meghah Vuppalapaty Timothy T Suen Chenggang Lu Yorick Post Yang Li BRAIDing receptors for cell-specific targeting eLife cell targeting WNT stem cell frizzled LRP induced proximity |
| title | BRAIDing receptors for cell-specific targeting |
| title_full | BRAIDing receptors for cell-specific targeting |
| title_fullStr | BRAIDing receptors for cell-specific targeting |
| title_full_unstemmed | BRAIDing receptors for cell-specific targeting |
| title_short | BRAIDing receptors for cell-specific targeting |
| title_sort | braiding receptors for cell specific targeting |
| topic | cell targeting WNT stem cell frizzled LRP induced proximity |
| url | https://elifesciences.org/articles/90221 |
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