Design of a synthesis‐friendly hypoxia‐responsive promoter for cell‐based therapeutics

Abstract Towards the goal of making ‘smart’ cell therapies, one that recognizes disease conditions (e.g. hypoxia) and then produces mitigating biologics, it is important to develop suitable promoters. Currently, hypoxia responsive promoters are composed of strongly repeated sequences containing hypo...

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Autores principales:	Chee Ka Candice Lam, Kevin Truong
Formato:	article
Lenguaje:	EN
Publicado:	Wiley-VCH 2021
Materias:	biosensor hypoxia inducible expression promoter design synthetic promoters Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/24ee11923f6240e090509d3fa57cb09b
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spelling	oai:doaj.org-article:24ee11923f6240e090509d3fa57cb09b2021-12-02T13:20:02ZDesign of a synthesis‐friendly hypoxia‐responsive promoter for cell‐based therapeutics1618-28631618-024010.1002/elsc.202100045https://doaj.org/article/24ee11923f6240e090509d3fa57cb09b2021-12-01T00:00:00Zhttps://doi.org/10.1002/elsc.202100045https://doaj.org/toc/1618-0240https://doaj.org/toc/1618-2863Abstract Towards the goal of making ‘smart’ cell therapies, one that recognizes disease conditions (e.g. hypoxia) and then produces mitigating biologics, it is important to develop suitable promoters. Currently, hypoxia responsive promoters are composed of strongly repeated sequences containing hypoxia response elements upstream of a minimal core promoter. Unfortunately, such repeated sequences have inherent genomic instability that may compromise the long‐term consistency of cell‐based therapeutics. Thus, we designed a synthesis‐friendly hypoxia‐inducible promoter (named SFHp) that has GC content between 25% and 75% and no repeats greater than 9 base pairs. In HEK293 cells stably integrated with genes regulated by synthetic SFHp, we demonstrated inducible reporter expression with fluorescent proteins, cell morphology rewiring with our previously engineered RhoA protein and intercellular cell signalling with secreted cytokines. These experiments exemplify the potential usage of SFHp in cell‐based therapeutics with integrated genetic circuits that inducibly respond to the disease microenvironment.Chee Ka Candice LamKevin TruongWiley-VCHarticlebiosensorhypoxiainducible expressionpromoter designsynthetic promotersBiotechnologyTP248.13-248.65ENEngineering in Life Sciences, Vol 21, Iss 12, Pp 848-856 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	biosensor hypoxia inducible expression promoter design synthetic promoters Biotechnology TP248.13-248.65
spellingShingle	biosensor hypoxia inducible expression promoter design synthetic promoters Biotechnology TP248.13-248.65 Chee Ka Candice Lam Kevin Truong Design of a synthesis‐friendly hypoxia‐responsive promoter for cell‐based therapeutics
description	Abstract Towards the goal of making ‘smart’ cell therapies, one that recognizes disease conditions (e.g. hypoxia) and then produces mitigating biologics, it is important to develop suitable promoters. Currently, hypoxia responsive promoters are composed of strongly repeated sequences containing hypoxia response elements upstream of a minimal core promoter. Unfortunately, such repeated sequences have inherent genomic instability that may compromise the long‐term consistency of cell‐based therapeutics. Thus, we designed a synthesis‐friendly hypoxia‐inducible promoter (named SFHp) that has GC content between 25% and 75% and no repeats greater than 9 base pairs. In HEK293 cells stably integrated with genes regulated by synthetic SFHp, we demonstrated inducible reporter expression with fluorescent proteins, cell morphology rewiring with our previously engineered RhoA protein and intercellular cell signalling with secreted cytokines. These experiments exemplify the potential usage of SFHp in cell‐based therapeutics with integrated genetic circuits that inducibly respond to the disease microenvironment.
format	article
author	Chee Ka Candice Lam Kevin Truong
author_facet	Chee Ka Candice Lam Kevin Truong
author_sort	Chee Ka Candice Lam
title	Design of a synthesis‐friendly hypoxia‐responsive promoter for cell‐based therapeutics
title_short	Design of a synthesis‐friendly hypoxia‐responsive promoter for cell‐based therapeutics
title_full	Design of a synthesis‐friendly hypoxia‐responsive promoter for cell‐based therapeutics
title_fullStr	Design of a synthesis‐friendly hypoxia‐responsive promoter for cell‐based therapeutics
title_full_unstemmed	Design of a synthesis‐friendly hypoxia‐responsive promoter for cell‐based therapeutics
title_sort	design of a synthesis‐friendly hypoxia‐responsive promoter for cell‐based therapeutics
publisher	Wiley-VCH
publishDate	2021
url	https://doaj.org/article/24ee11923f6240e090509d3fa57cb09b
work_keys_str_mv	AT cheekacandicelam designofasynthesisfriendlyhypoxiaresponsivepromoterforcellbasedtherapeutics AT kevintruong designofasynthesisfriendlyhypoxiaresponsivepromoterforcellbasedtherapeutics
_version_	1718393258819715072

Design of a synthesis‐friendly hypoxia‐responsive promoter for cell‐based therapeutics

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