Engineering APOBEC3A deaminase for highly accurate and efficient base editing

Anzalone, A. V., Koblan, L. W. & Liu, D. R. Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors. Nat. Biotechnol. 38, 824–844 (2020).

Gaudelli, N. M. et al. Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature 551, 464–471 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Komor, A. C., Kim, Y. B., Packer, M. S., Zuris, J. A. & Liu, D. R. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533, 420–424 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhao, D. D. et al. New base editors change C to A in bacteria and C to G in mammalian cells. Nat. Biotechnol. 39, 35–40 (2021).

Article  CAS  PubMed  Google Scholar 

Kurt, I. C. et al. CRISPR C-to-G base editors for inducing targeted DNA transversions in human cells. Nat. Biotechnol. 39, 41–46 (2021).

Article  CAS  PubMed  Google Scholar 

Kim, K. et al. Highly efficient RNA-guided base editing in mouse embryos. Nat. Biotechnol. 35, 435–437 (2017).

Article  CAS  PubMed  Google Scholar 

Yang, L. et al. Increasing targeting scope of adenosine base editors in mouse and rat embryos through fusion of TadA deaminase with Cas9 variants. Protein Cell 9, 814–819 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Zong, Y. et al. Efficient C-to-T base editing in plants using a fusion of nCas9 and human APOBEC3A. Nat. Biotechnol. 36, 950–953 (2018).

Article  CAS  Google Scholar 

Shimatani, Z. et al. Targeted base editing in rice and tomato using a CRISPR-Cas9 cytidine deaminase fusion. Nat. Biotechnol. 35, 441–443 (2017).

Article  CAS  PubMed  Google Scholar 

Villiger, L. et al. Treatment of a metabolic liver disease by in vivo genome base editing in adult mice. Nat. Med. 24, 1519–1525 (2018).

Article  CAS  PubMed  Google Scholar 

Rossidis, A. C. et al. In utero CRISPR-mediated therapeutic editing of metabolic genes. Nat. Med. 24, 1513–1518 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li, G. L. et al. Gene editing and its applications in biomedicine. Sci. China Life Sci. 65, 660–700 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zuo, E. et al. Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos. Science 364, 289–292 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jin, S. et al. Cytosine, but not adenine, base editors induce genome-wide off-target mutations in rice. Science 364, 292–295 (2019).

Article  CAS  PubMed  Google Scholar 

Grunewald, J. et al. Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors. Nature 569, 433–437 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhou, C. et al. Off-target RNA mutation induced by DNA base editing and its elimination by mutagenesis. Nature 571, 275–278 (2019).

Article  CAS  PubMed  Google Scholar 

Rothgangl, T. et al. In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels. Nat. Biotechnol. 39, 949–957 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tan, J. J., Zhang, F., Karcher, D. & Bock, R. Engineering of high-precision base editors for site-specific single nucleotide replacement. Nat. Commun. 10, 439 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gehrke, J. M. et al. An APOBEC3A-Cas9 base editor with minimized bystander and off-target activities. Nat. Biotechnol. 36, 977–982 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lee, S. et al. Single C-to-T substitution using engineered APOBEC3G-nCas9 base editors with minimum genome- and transcriptome-wide off-target effects. Sci. Adv. 6, eaba1773 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim, Y. B. et al. Increasing the genome-targeting scope and precision of base editing with engineered Cas9-cytidine deaminase fusions. Nat. Biotechnol. 35, 371–376 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zuo, E. et al. A rationally engineered cytosine base editor retains high on-target activity while reducing both DNA and RNA off-target effects. Nat. Methods 17, 600–604 (2020).

Article  CAS  PubMed  Google Scholar 

Wang, L. et al. Eliminating base-editor-induced genome-wide and transcriptome-wide off-target mutations. Nat. Cell Biol. 23, 552–563 (2021).

Article  PubMed  Google Scholar 

Wang, X. et al. Efficient base editing in methylated regions with a human APOBEC3A-Cas9 fusion. Nat. Biotechnol. 36, 946–949 (2018).

Article  CAS  PubMed  Google Scholar 

Doman, J. L., Raguram, A., Newby, G. A. & Liu, D. R. Evaluation and minimization of Cas9-independent off-target DNA editing by cytosine base editors. Nat. Biotechnol. 38, 620–628 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shi, K. et al. Structural basis for targeted DNA cytosine deamination and mutagenesis by APOBEC3A and APOBEC3B. Nat. Struct. Mol. Biol. 24, 131–139 (2017).

Article  CAS  PubMed  Google Scholar 

Kouno, T. et al. Crystal structure of APOBEC3A bound to single-stranded DNA reveals structural basis for cytidine deamination and specificity. Nat. Commun. 8, 15024 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Koblan, L. W. et al. Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction. Nat. Biotechnol. 36, 843–846 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nishimasu, H. et al. Engineered CRISPR-Cas9 nuclease with expanded targeting space. Science 361, 1259–1262 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tsai, S. Q. et al. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nat. Biotechnol. 33, 187–197 (2015).

Article  CAS  PubMed  Google Scholar 

Sharma, S. et al. APOBEC3A cytidine deaminase induces RNA editing in monocytes and macrophages. Nat. Commun. 6, 6881 (2015).

Article  CAS  PubMed  Google Scholar 

Andreucci, E. et al. TRPV4 related skeletal dysplasias: a phenotypic spectrum highlighted byclinical, radiographic, and molecular studies in 21 new families. Orphanet J. Rare Dis. 6, 37 (2011).

Article  PubMed  PubMed Central  Google Scholar 

Dorval, I. et al. Analysis of 160 CF chromosomes: detection of a novel mutation in exon 20. Hum. Genet 91, 254–256 (1993).

Article  CAS  PubMed  Google Scholar 

Higuchi, M. et al. Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the Factor VIII gene. Proc. Natl Acad. Sci. USA 88, 7405–7409 (1991).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cuesta-Munoz, A. L. et al. Severe persistent hyperinsulinemic hypoglycemia due to a de novo glucokinase mutation. Diabetes 53, 2164–2168 (2004).

Article  CAS  PubMed  Google Scholar 

Hermans, M. M. et al. Twenty-two novel mutations in the lysosomal alpha-glucosidase gene (GAA) underscore the genotype-phenotype correlation in glycogen storage disease type II. Hum. Mutat. 23, 47–56 (2004).

Article  CAS  PubMed  Google Scholar 

Guldberg, P. et al. A novel missense mutation in the phenylalanine hydroxylase gene of a homozygous Pakistani patient with non-PKU hyperphenylalaninemia. Hum. Mol. Genet 2, 1061–1062 (1993).

Article  CAS  PubMed  Google Scholar 

Janecke, A. R. et al. Mutations in RDH12 encoding a photoreceptor cell retinol dehydrogenase cause childhood-onset severe retinal dystrophy. Nat. Genet. 36, 850–854 (2004).

Comments (0)

No login
gif