Home NATURALEZA Engineering a photoactivatable A-to-I RNA base editor for gene therapy in vivo

Engineering a photoactivatable A-to-I RNA base editor for gene therapy in vivo

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  • Doudna, J. A. The promise and challenge of therapeutic genome editing. Nature 578, 229–236 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pacesa, M., Pelea, O. & Jinek, M. Past, present, and future of CRISPR genome editing technologies. Cell 187, 1076–1100 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhong, G. et al. A reversible RNA on-switch that controls gene expression of AAV-delivered therapeutics in vivo. Nat. Biotechnol. 38, 169–175 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Monteys, A. M. et al. Regulated control of gene therapies by drug-induced splicing. Nature 596, 291–295 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, R. et al. Optogenetic control of RNA function and metabolism using engineered light-switchable RNA-binding proteins. Nat. Biotechnol. 40, 779–786 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Pfeiffer, L. S. & Stafforst, T. Precision RNA base editing with engineered and endogenous effectors. Nat. Biotechnol. 41, 1526–1542 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Booth, B. J. et al. RNA editing: expanding the potential of RNA therapeutics. Mol. Ther. 31, 1533–1549 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Song, J., Zhuang, Y. & Yi, C. Programmable RNA base editing via targeted modifications. Nat. Chem. Biol. 20, 277–290 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Merkle, T. et al. Precise RNA editing by recruiting endogenous ADARs with antisense oligonucleotides. Nat. Biotechnol. 37, 133–138 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Qu, L. et al. Programmable RNA editing by recruiting endogenous ADAR using engineered RNAs. Nat. Biotechnol. 37, 1059–1069 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Reautschnig, P. et al. CLUSTER guide RNAs enable precise and efficient RNA editing with endogenous ADAR enzymes in vivo. Nat. Biotechnol. 40, 759–768 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Katrekar, D. et al. Efficient in vitro and in vivo RNA editing via recruitment of endogenous ADARs using circular guide RNAs. Nat. Biotechnol. 40, 938–945 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Vogel, P. et al. Efficient and precise editing of endogenous transcripts with SNAP-tagged ADARs. Nat. Methods 15, 535–538 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Montiel-Gonzalez, M. F., Vallecillo-Viejo, I., Yudowski, G. A. & Rosenthal, J. J. C. Correction of mutations within the cystic fibrosis transmembrane conductance regulator by site-directed RNA editing. Proc. Natl Acad. Sci. USA 110, 18285–18290 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Han, W. et al. Programmable RNA base editing with a single gRNA-free enzyme. Nucleic Acids Res. 50, 9580–9595 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cox, D. B. T. et al. RNA editing with CRISPR-Cas13. Science 358, 1019–1027 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kannan, S. et al. Compact RNA editors with small Cas13 proteins. Nat. Biotechnol. 40, 194–197 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Xu, C. et al. Programmable RNA editing with compact CRISPR–Cas13 systems from uncultivated microbes. Nat. Methods 18, 499–506 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rauch, S. et al. Programmable RNA-guided RNA effector proteins built from human parts. Cell 178, 122–134.e12 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rauch, S., Jones, K. A. & Dickinson, B. C. Small molecule-inducible RNA-targeting systems for temporal control of RNA regulation. ACS Cent. Sci. 6, 1987–1996 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Stroppel, A. S., Lappalainen, R. & Stafforst, T. Controlling site-directed RNA editing by chemically induced dimerization. Chemistry 27, 12300–12304 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, Y. et al. Light-triggered site-directed RNA editing by endogenous ADAR1 with photolabile guide RNA. Cell Chem. Biol. 30, 672–682.e5 (2023).

    Article 
    CAS 

    Google Scholar
     

  • Hanswillemenke, A., Kuzdere, T., Vogel, P., Jékely, G. & Stafforst, T. Site-directed RNA editing in vivo can be triggered by the light-driven assembly of an artificial riboprotein. J. Am. Chem. Soc. 137, 15875–15881 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bennett, C. F., Baker, B. F., Pham, N., Swayze, E. & Geary, R. S. Pharmacology of antisense drugs. Annu. Rev. Pharmacol. Toxicol. 57, 81–105 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yu, J. et al. Programmable RNA base editing with photoactivatable CRISPR-Cas13. Nat. Commun. 15, 673 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kawano, F., Suzuki, H., Furuya, A. & Sato, M. Engineered pairs of distinct photoswitches for optogenetic control of cellular proteins. Nat. Commun. 6, 6256 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Katrekar, D. et al. Comprehensive interrogation of the ADAR2 deaminase domain for engineering enhanced RNA editing activity and specificity. Elife 11, 1–19 (2022).

    Article 

    Google Scholar
     

  • Wong, S. K., Sato, S. & Lazinski, D. W. Substrate recognition by ADAR1 and ADAR2. RNA 7, 846–858 (2001).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Konermann, S. et al. Transcriptome engineering with RNA-targeting type VI-D CRISPR effectors. Cell 173, 665–676.e14 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Paulmurugan, R. & Gambhir, S. S. Combinatorial library screening for developing an improved split-firefly luciferase fragment-assisted complementation system for studying protein–protein interactions. Anal. Chem. 79, 2346–2353 (2007).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, H. et al. Efficient photoactivatable Dre recombinase for cell type-specific spatiotemporal control of genome engineering in the mouse. Proc. Natl Acad. Sci. USA 117, 33426–33435 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, H. et al. Stable transgenic mouse strain with enhanced photoactivatable Cre recombinase for spatiotemporal genome manipulation. Adv. Sci. 9, 1–12 (2022).

    Article 
    CAS 

    Google Scholar
     

  • Kuttan, A. & Bass, B. L. Mechanistic insights into editing-site specificity of ADARs. Proc. Natl Acad. Sci. USA 109, E3295–E3304 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, X. et al. Develop a compact RNA base editor by fusing ADAR with engineered EcCas6e. Adv. Sci. 10, 1–8 (2023).


    Google Scholar
     

  • Benedetti, L. et al. Optimized vivid-derived magnets photodimerizers for subcellular optogenetics in mammalian cells. Elife 9, 1–49 (2020).

    Article 

    Google Scholar
     

  • Martins-Dias, P. & Romão, L. Nonsense suppression therapies in human genetic diseases. Cell. Mol. Life Sci. 78, 4677–4701 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Luo, N. et al. Near-cognate tRNAs increase the efficiency and precision of pseudouridine-mediated readthrough of premature termination codons. Nat. Biotechnol. 43, 114–123 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Albers, S. et al. Engineered tRNAs suppress nonsense mutations in cells and in vivo. Nature 618, 842–848 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yi, Z. et al. Engineered circular ADAR-recruiting RNAs increase the efficiency and fidelity of RNA editing in vitro and in vivo. Nat. Biotechnol. 40, 946–955 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • MacDonald, B. T., Tamai, K. & He, X. Wnt/β-catenin signaling: components, mechanisms, and diseases. Dev. Cell 17, 9–26 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, C. et al. Control of β-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108, 837–847 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kay, M. A., He, C.-Y. & Chen, Z.-Y. A robust system for production of minicircle DNA vectors. Nat. Biotechnol. 28, 1287–1289 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lamb, Y. N. & Hoy, S. M. Eftrenonacog alfa: a review in haemophilia B. Drugs 83, 807–818 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nathwani, A. C. et al. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N. Engl. J. Med. 371, 1994–2004 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • George, L. A. et al. Hemophilia B gene therapy with a high-specific-activity factor IX variant. N. Engl. J. Med. 377, 2215–2227 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kaczmarek, R. & Herzog, R. W. Treatment-induced hemophilic thrombosis? Mol. Ther. 30, 505–506 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Simioni, P. et al. X-linked thrombophilia with a mutant factor IX (factor IX Padua). N. Engl. J. Med. 361, 1671–1675 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Guan, Y. et al. CRISPR/Cas9‐mediated somatic correction of a novel coagulator factor IX gene mutation ameliorates hemophilia in mouse. EMBO Mol. Med. 8, 477–488 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Anadón, C. et al. Gene amplification-associated overexpression of the RNA editing enzyme ADAR1 enhances human lung tumorigenesis. Oncogene 35, 4407–4413 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Teoh, P. J. et al. Aberrant hyperediting of the myeloma transcriptome by ADAR1 confers oncogenicity and is a marker of poor prognosis. Blood 132, 1304–1317 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nguyen, N. T. et al. Nano-optogenetic engineering of CAR T cells for precision immunotherapy with enhanced safety. Nat. Nanotechnol. 16, 1424–1434 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang, Z. et al. Engineering light-controllable CAR T cells for cancer immunotherapy. Sci. Adv. 6, 1–14 (2020).

    Article 

    Google Scholar
     

  • Bansal, A., Shikha, S. & Zhang, Y. Towards translational optogenetics. Nat. Biomed. Eng. 7, 349–369 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Zhou, Y. et al. A small and highly sensitive red/far-red optogenetic switch for applications in mammals. Nat. Biotechnol. 40, 262–272 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kuwasaki, Y. et al. A red light-responsive photoswitch for deep tissue optogenetics. Nat. Biotechnol. 40, 1672–1679 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bonger, K. M., Chen, L., Liu, C. W. & Wandless, T. J. Small-molecule displacement of a cryptic degron causes conditional protein degradation. Nat. Chem. Biol. 7, 531–537 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hwang, G.-H. et al. Web-based design and analysis tools for CRISPR base editing. BMC Bioinformatics 19, 542 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, H. et al. Engineering a photoactivatable A-to-I RNA base editor for gene therapy in vivo. NCBI SRA https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1194220 (2025).

  • Li, H. et al. Engineering a photoactivatable A-to-I RNA base editor for gene therapy in vivo. NCBI SRA https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1194292 (2025).

  • Li, H. et al. Engineering a photoactivatable A-to-I RNA base editor for gene therapy in vivo. NCBI SRA https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1197542 (2025).

  • Li, H. et al. Engineering a photoactivatable A-to-I RNA base editor for gene therapy in vivo. NCBI SRA https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1207784 (2025).

  • Li, H. et al. Engineering a photoactivatable A-to-I RNA base editor for gene therapy in vivo. NCBI SRA https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1194549 (2025).

  • Li, H. et al. Engineering a photoactivatable A-to-I RNA base editor for gene therapy in vivo. NCBI SRA https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1207789 (2025).



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