Model-guided design of microRNA-based gene circuits supports precise dosage of transgenic cargoes into diverse primary cells DOI Creative Commons
Kasey S. Love, Christopher P. Johnstone, Emma L. Peterman

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 25, 2024

Abstract To realize the potential of engineered cells in therapeutic applications, transgenes must be expressed within window efficacy. Differences copy number and other sources extrinsic noise generate variance transgene expression limit performance synthetic gene circuits. In a context, supraphysiological can compromise phenotypes lead to toxicity. ensure narrow range expression, we design characterize Co mpact m icroRNA- M ediated A ttenuator N oise D osage ( ComMAND ), single-transcript, microRNA-based incoherent feedforward loop. We experimentally tune output profile, model system explore additional tuning strategies. By comparing two-gene implementations, highlight precise control afforded by single-transcript architecture, particularly at relatively low numbers. show that tightly regulates from lentiviruses precisely controls primary human T cells, rat neurons, mouse embryonic fibroblasts, induced pluripotent stem cells. Finally, effectively sets levels clinically relevant FMRP1 FXN window. Together, is compact tool well-suited specify cargoes.

Язык: Английский

Integrating bioelectronics with cell-based synthetic biology DOI
Jonathan Rivnay, Ritu Raman, Jacob T. Robinson

и другие.

Nature Reviews Bioengineering, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Язык: Английский

Процитировано

3

Compact transcription factor cassettes generate functional, engraftable motor neurons by direct conversion DOI
Nathan Wang, Honour O Adewumi, Brittany A Lende-Dorn

и другие.

Cell Systems, Год журнала: 2025, Номер unknown, С. 101206 - 101206

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

1

STRAIGHT-IN Dual: a platform for dual, single-copy integrations of DNA payloads and gene circuits into human induced pluripotent stem cells DOI Creative Commons
Albert Blanch-Asensio, Deon Ploessl, Nathan Wang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 17, 2024

Abstract Targeting DNA payloads into human (h)iPSCs involves multiple time-consuming, inefficient steps that must be repeated for each construct. Here, we present STRAIGHT-IN Dual, which enables simultaneous, allele-specific, single-copy integration of two with 100% efficiency within one week. Notably, Dual leverages the platform to allow near-scarless cargo integration, facilitating recycling components subsequent cellular modifications. Using investigated how promoter choice and gene syntax influences transgene silencing, demonstrate impact these design features on forward programming hiPSCs neurons. Furthermore, designed a grazoprevir-inducible synZiFTR system complement widely-used tetracycline-inducible system, providing independent, tunable, temporally controlled expression both transcription factors functional reporters. The unprecedented speed generates homogenous genetically engineered hiPSC populations represents major advancement synthetic biology in stem cell applications opens opportunities precision engineering.

Язык: Английский

Процитировано

4

Designer mammalian living materials through genetic engineering DOI
Mariana Gameiro, J. Almeida-Pinto, Beatriz S. Moura

и другие.

Bioactive Materials, Год журнала: 2025, Номер 48, С. 135 - 148

Опубликована: Фев. 15, 2025

Язык: Английский

Процитировано

0

Model-guided design of microRNA-based gene circuits supports precise dosage of transgenic cargoes into diverse primary cells DOI Creative Commons
Kasey S. Love, Christopher P. Johnstone, Emma L. Peterman

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 25, 2024

Abstract To realize the potential of engineered cells in therapeutic applications, transgenes must be expressed within window efficacy. Differences copy number and other sources extrinsic noise generate variance transgene expression limit performance synthetic gene circuits. In a context, supraphysiological can compromise phenotypes lead to toxicity. ensure narrow range expression, we design characterize Co mpact m icroRNA- M ediated A ttenuator N oise D osage ( ComMAND ), single-transcript, microRNA-based incoherent feedforward loop. We experimentally tune output profile, model system explore additional tuning strategies. By comparing two-gene implementations, highlight precise control afforded by single-transcript architecture, particularly at relatively low numbers. show that tightly regulates from lentiviruses precisely controls primary human T cells, rat neurons, mouse embryonic fibroblasts, induced pluripotent stem cells. Finally, effectively sets levels clinically relevant FMRP1 FXN window. Together, is compact tool well-suited specify cargoes.

Язык: Английский

Процитировано

3