A far-red light–inducible CRISPR-Cas12a platform for remote-controlled genome editing and gene activation

Wang, Xinyi; Dong, Kaili; Kong, Dan; Zhou, Yang; Yin, Jianli; Cai, Fengfeng; Wang, Meiyan

doi:10.1126/sciadv.abh2358

Cited by 22 publications

(22 citation statements)

References 65 publications

(79 reference statements)

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“…Besides, optogenetics provides a promising approach for gene-and cell-based therapies via precisely manipulating various cellular activities with high spatiotemporal resolution [63]. And the deep tissue penetration of NIR light offers a non-invasive treatment modality for a variety of diseases [64,65]. The illumination intensity and pattern of multiple light spots, especially lasers, can be easily controlled by computer algorithms, enabling neuroscientists to stimulate hundreds of precisely targeted neurons simultaneously [66].…”

Section: Discussionmentioning

confidence: 99%

Programming the lifestyles of engineered bacteria for cancer therapy

Zhang

Gao

et al. 2022

Preprint

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Bacteria can be genetically engineered to act as therapeutic delivery vehicles in the treatment of tumors, killing cancer cells or activating the immune system. This is known as Bacteria-Mediated Cancer Therapy (BMCT). Tumor invasion, colonization and tumor regression are major biological events, which are directly associated with antitumor effects and are uncontrollable due to the influence of tumor microenvironments during the BMCT process. Here, we developed a genetic circuit for dynamically programming bacterial lifestyles (planktonic, biofilm or lysis), to precisely manipulate the process of bacterial adhesion, colonization and drug release in BMCT process, via hierarchical modulation of the lighting power density (LPD) of near-infrared (NIR) light. The deep tissue penetration of NIR offers us a modality for spatiotemporal and noninvasive control of bacterial genetic circuits in vivo. By combining computational modeling with high throughput characterization device, we optimized the genetic circuits in engineered bacteria to program the process of bacterial lifestyle transitions by altering the illumination scheme of NIR. Our results showed that programming intratumoral bacterial lifestyle transitions allows precise control of multiple key steps throughout the BMCT process, and therapeutic efficacy can be greatly improved by controlling the localization and dosage of therapeutic agents via optimizing the illumination scheme.

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Section: Discussionmentioning

confidence: 99%

Programming the lifestyles of engineered bacteria for cancer therapy

Zhang

Gao

et al. 2022

Preprint

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“…OPEN ACCESS Opto-CRAC and CaRROT for Ca 2+ -dependent transcriptional activation [14,[83][84][85][86]; LiCre for photoactivatable DNA recombination [59]; LiCASINO [93] or CASANOVA [97] mRNA-LARIAT for mRNA perturbation and relocalization [111].…”

Section: Trends In Geneticsmentioning

confidence: 99%

Optogenetics for transcriptional programming and genetic engineering

Lan

Huang

et al. 2022

Trends in Genetics

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“…Taking advantage of this photochemical feature, the Ye group at East China Normal University developed smartphone‐controlled optogenetically engineered cells to enable semi‐automatic control of blood glucose levels in diabetic mice, which sets the stage for translating cell‐based therapies for diabetes intervention. 6 In addition, combined with CRISPR/Cas12a 7 or CRISPR/dCas9 8 , BphS was further harnessed to manipulate target gene expression at endogenous genomic loci. Nevertheless, the requirement of prolonged light illumination and the immunostimulatory effect of c‐di‐GMP make this type of optogenetic device face multiple translational barriers.…”

Section: Where We Stand With Red‐shifted Optogeneticsmentioning

confidence: 99%