Base editor can induce specific base changes without DSBs and donor templates, which make it a convenient, high-efficiency approach for engineering nucleotide substitutions at target sites. Firstly, ABEs bind the target DNA guided by sgRNA. Moreover, they used phage-assisted continuous evolution method to evolve a new SpCas9 variant (xCas9) with an expanded PAM including NG, GAA, and GAT [28]. And a mismatched cytidine in the crRNA opposite the target adenosine could enhance the editing reaction [46] (Figure 3). 10.Responsible for … Fang Wang, Yuqiang Zeng, Yi Wang, Yuyu Niu, "The Development and Application of a Base Editor in Biomedicine", BioMed Research International, vol. New Window /In female FIscher rats/ Blood levels after iv injection appear to decay in a triphasic manner with half-lives of 0.19 +/- 0.11 hrs, 6.6 +/- 3.9 hrs, and 117 +/- 47 hrs. These variants not only expand the editable range but also improve the editing efficiency of target sites (Table 1). The first explosive event about gene editing came from Scherer and Davis in 1979, who develop a method that could be used to introduce foreign sequences into the chromosomes of yeast [1]. The groups of Jiang and coworkers developed base editor (BE-PLUS) with expanded C to U (T) programming scope [27]. S2). be3 Human Resource Management Pvt Ltd 3 years 11 months Sr.Hr executive ... Be the one point of contact for all the grievances related to the employee life cycle. Life Plus Hospital is one of the Best Obstetrics & Gynecologist Hospital in Bangalore. Tough & Trusted. Geurts and coworkers applied SpCas9-ABE and xCas9-ABE on four cystic fibrosis (CF) organoid sample. Edge, and D. R. Liu, “In vivo base editing of post-mitotic sensory cells,”. At the same time, RNA editing can also help us interrogate genes and noncoding RNA as well as control cellular processes at the transcript level. RERAIR includes a catalytically dead RNA-guided Cas13b enzyme (dPspCas13b), an ADAR, and a sgRNA. Significantly, the three teams all demonstrated that the absence of sgRNA did not change the levels of nonspecific off-target edited by CBEs. Watch them all exclusively with Disney+ Hotstar Twice Nation. In 2016, Komor et al. Extract transfection-quality plasmids for your gRNA and base editor of choice. Park et al., “Digenome-seq: genome-wide profiling of CRISPR-Cas9 off-target effects in human cells,”, D. Kim, K. Lim, S. T. Kim et al., “Genome-wide target specificities of CRISPR RNA-guided programmable deaminases,”, D. Kim, D. E. Kim, G. Lee, S. I. Cho, and J. S. Kim, “Genome-wide target specificity of CRISPR RNA-guided adenine base editors,”, W. H. Yeh, H. Chiang, H. A. Rees, A. S. B. We have a team of highly experienced Obstetrician & Gynaecologists in Bangalore. Copyright © 2020 Fang Wang et al. Home › Fujitsu › Arrows Be3 F-02L. iTerm Plan Online - Term insurance premium for Aegon Life iTerm Plan which now covers COVID-19 death Claims as well. Surprisingly, the number of SNVs in embryos edited by CBEs was over 20-fold higher than that in others. Using it, they assess the specificity of 25 rationally designed A3Bctd-BE3s, identifying A3Bctd-VHM-BE3 and A3Bctd-KKR-BE3 with high specificity and precision. Recently, Richter and coworkers developed a new ABE variant—ABE8e—which activity has been increased 590-fold than ABE7.10’s. The random indels around the cleavage sites are generally more abundant than gene replacement giving that the DSBs are preferentially repaired by nonhomologous end joining (NHEJ) in cells [6, 14]. Subsequently, they modified the base editor by installing mutations into third-generation base editor (HF-BE3) [ 16 Predictably, if the base editor stays in the cell too long, it will cause more off-target. Overview of different base editor variants. Nirvana Group … For more information about our services, visit: www.thelifeplushospital.com # LifePlusHospital # DrBhargaviReddy # Gynecologist … With the emergence of CBEs, other two teams reported new base editor-targeted AID-mediated mutagenesis (TAM). Their studies showed that both genetic mutations and functional disorders were repaired in all four cases, indicating that 20% of 664 patients in CF intestinal organoid biobank can be repaired by ABE [80]. Cell proliferation/viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5 … For example, take the stairs instead of the elevator, stand at your desk instead of sitting, walk in place during your favorite TV show, or park at the back of the lot when you go shopping. Nevertheless, the predictions are usually far different from the WGS—a cumbersome and expensive approach. 2600 mAh (Li-Ion) BLU Studio Mega 2018. When there are multiple editable Cs or As within or nearby the “editing window” (positions 4-8 for CBE or 4-7 for ABE, counting the PAM as positions 21-23), base editor could induce the conversion of bases edit in addition to the target base. Information about the battery capacity and battery life of the Fujitsu Arrows Be3 F-02L. B. Kim, M. S. Packer, J. Indel formation: ≤ 5 % Off-target editing: high genome-wide, rAPOBEC1-XTEN-dCas9(A840H, N497A, R661A, Q695A and Q926A)-UGI, Apparent editing efficiency: 30-40% (in vitro) 20-25% (in vivo). Therefore, using the preassembled CRISPR/Cas9 RNPs with sgRNA can reduce possible off-target mutations due to the short half-life [16, 106, 107]. However, this approach induces marked toxicity and show sensitivity in specific cell that limit the application. Dimensions: 70 x 147 x 8.9 mm Weight: … Thus, BE3 is rAPOBEC1-XTEN-dCas9 (A840H)-UGI, or rAPOBEC1-XTEN-dCas9nickase-UGI, an enzyme unable to cleave dsDNA (Cas9 retains the D10A mutation) but can nick the non-edited strand [ 3 ]. N. Jakimo, P. Chatterjee, L. Nip, and J. M. Jacobson, “A Cas9 with complete PAM recognition for adenine dinucleotides,” 2018. In this review, we will elaborate the development and application of a base editor in gene therapy. The advantages are nongenomic integration and broad tissue targeting possibilities. 2750 mAh (Li-Polymer) BLU G6. Harmony Grins. They utilized CjABE to correct the 124C>T TERT promoter mutation. Health/Beauty. BLU Life View. Ran, D. Cox et al., “Multiplex genome engineering using CRISPR/Cas systems,”, P. Mali, L. Yang, K. M. Esvelt et al., “RNA-guided human genome engineering via Cas9,”, M. Jinek, A. Summary of application of base editor in gene therapy. CrRNA is targeted to the specific site by hybridization to create a dsRNA structure and recruit dCas13b-ADARDD. They injected dual AAV particles encoding a split-intein CBE, introducing a nonsense-conding substitution into a mutant SOD1G93A, and achieving significantly slowed progression of ALS disease in mouse model [78]. 8.3 Biological Half-Life. Sun, R. Yan et al., “Off-target RNA mutation induced by DNA base editing and its elimination by mutagenesis,”, S. Bae, J. Science. ABEs is composed of the fusion of TadA (wild type) and TadA. In 2017, Shmakov’s team developed a precise and flexible technology, Programmable adenosine to inosine Replacement (REPAIR), in RNA level by using the type VI CRISPR-associated RNA-guided RNase Cas13 [43–45]. Mol Plant. A, Root growth of 5-d-old wild type (WT) and T3 progenies of BE3-CESA3 S983F (S983F) and BE3 … We thank Dr. Qiaoyan Yang from the Leon H Charney Division of Cardiology, New York University School of Medicine, for helpful suggestions and modifications to this manuscript. Based on this property of CRISPR/Cas9, scientists have developed a variety of derivatives according to different gene editing requirements. Send a 3GB 4K UHD video file from your FIT Plus to your PC in just 10 seconds². Further, verifying the safety of base editor in clinical gene therapy, researchers are now focusing on human embryos and cells. As a burgeoning approach for genomic modification, the fused CRISPR/Cas9 with various deaminase separately has significantly increased the efficiency of producing a precise point mutation with minimal insertions or deletions (indels). Conversely, in some cases, the editing windows need to be expanded to achieve targeted base editing. 1 Up to 72 … All the variants hold great potential for both basic research and clinical application in biomedicine. Product/Service. Search the world's information, including webpages, images, videos and more. Although both of them demonstrated the potentiality of therapeutic genome editing, they required a lot of time and labor. So, we need to develop reliable predictive software. Huang’s studies proved that using base editor in anemia could not only cure the disease but also prevent the disease from being passed onto future generations. optimized the nuclear localization signals (NLS) and codon usage, as well as reconstructed the ancestral deaminase component [20]. All of the studies warm us to seriously consider the problem of off-target before clinical therapy. C17 tolerance induced by the BE3-CESA3 S983F vector could be inherited. In addition, in order to overcome the defect that conventional CRISPR/Cas9 induced abundant and unpredictable insertions or deletions (indels) and exhibited low efficiency in correcting point mutations, researchers developed a base editor—a new elegant Cas9 derivative which could efficiently generate precise point mutations with minimal indels. And it had been confirmed that there are 83% of existing TERT (124C>T) mutation lesions in GBM [81]. Disney+ is the one-stop destination for your favorite movies and series from Disney, Pixar, Marvel, Star Wars and National Geographic. Moreover, two team demonstrated new CBE variant (eA3A-BE3) which replaced the regular cytidine deaminases—rAPOBEC1 with human APOBEC3A—that have narrower editing windows that can reduce bystander mutations and mediate efficient C to T conversion in regions with high methylation levels [30, 31]. They developed a base editor variant which is composed of an nCas9 of Campylobacter jujuni and an adenine base editor (CjABE). Due to the property of deaminases which can modify RNA and single-stranded DNA at sites other than the intended target, the base editor can alter the DNA. Benefit from the progress of gene therapy, we are entering an era in which genome editing tools could be used to manipulate gene sequences flexibly and precisely. Titus Pinto is on Facebook. Quantifying base editing efficiency using high-throughput sequencing. SNAP-ADAR2DD + chemically modified anti-sense RNA, ADAR2 + RNA fusion: 5’ R/G-binding motif hairpin- native binding sequence of ADAR2- antisense-RNA, dPspCas13b- ADAR2DD(E488Q) + gRNA with central A:C mismatch, dPspCas13b- ADAR2DD(E488Q/T375G) + gRNA with central A:C mismatch, dPspCas13b- evolvedADAR2DD(E488Q/T375G) + gRNA with central A:C mismatch, Design the guide RNA of targeting the site of interest. However, when a single target nucleotide is present within the base editing window, or when bystander edits are acceptable, primer editor is little efficient and generate more indels than current base editor. Except in DNA level, base editing in RNA can also provide powerful capabilities for life sciences. Onision has gotten his very own documentary on on Discovery+. This review will focus on the modeling and treatment of different disease to describe the prospect of base editor in biomedicine. Notably, the different forms of base editor also affect editing efficiency. Two studies in nature medicine demonstrated that the base editor could be used to treat genetic disease in mice model of human autosomal recessive liver disease phenylketonuria or hereditary tyrosinemia type 1 [76, 77]. Many gRNA empty vectors have been deposited at Addgene (https://www.addgene.org/crispr/empty-grna-vectors/). 2800 mAh (Li-Ion) BLU Neo XL. Either narrower or broader strategy both enlarged the genome-targeting scope. Shopping & Retail. Subsequently, the development of clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) offers a simpler technology which has been adopted widely, owing to its easier DNA-binding and modifying capabilities [5, 6]. Note that the presence of Cas9 protein is also required. Fang Wang and Yuqiang Zeng contributed equally to this work. They fused activation-induced cytidine deaminase (AID) or AID ortholog PmCDA1 with nuclease-inactive CRISPR/Cas9 for efficient genetic modifications, which enabled to perform highly efficient site-directed mutagenesis and high-throughput screening of functional variants [21–23]. The new variants retain the substrate-targeting scope of high-activity CBEs as well as maintain minimal numbers of Cas9-independent off-targets [98]. Recently, the team of Doman focused on the deaminase domain of APOBEC1 and engineered YE1 variants to narrow the on-target base editing window by screening of deaminase mutant. To solve this problem, researchers further optimized the cytidine deaminase domains via inducing specific mutations, which eventually narrowed the width of the editing window from ~5 nucleotides to as little as 1-2 nucleotides [24]. Jin’s team demonstrated that CBEs but not ABE induced substantial genome-wide off-target mutations which were mostly the C to T conversion by comparing the WGS results from rice plants edited by CBEs (BE3 and HF-BE3) or the ABE, with unedited population as control [90]. Then, researchers continuously finished precise gene targeting by homologous recombination in Drosophila [2], mouse [3], and human [4]. Jin et al. Both BE3 and hA3A-BE3 yielded a higher C-to-T fraction at CpG sites with high methylation status than at CpG sites with low methylation status (Supplementary Fig. We are given the energy level (n) of the electron present in Be3+ B e 3 +. Last year, two papers in science both reported the high levels of genome-wide off-target effects by CBEs [90, 91]. They used CBEs to induce C to T conversion to generate a premature stop codon in Mstn and Tyr gene, respectively, and obtained two models that were double-muscled and albinism diseases. To broaden the targetable genome sequences of base editor, scientists have exploited numbers of Cas9 variants or homologue. The BE2 consists of three components, including a catalytically inactivated Cas9 (dCas9) derived from Streptococcus pyogenes Cas9 (SpCas9), a cytidine deaminase-APOBEC1, and an inhibitor of base excision repair-uracil glycosylase inhibitor (UGI). Intriguingly, Liu and coworkers created mouse model harboring multiple mutations by using a combination of ABE and SaBE3. rAPOBEC1-32aa linker-dCas9(A840H) nickase-9aa linker-UGI-9aa linker-UGI, Apparent editing efficiency: ~50% (in vivo); Indel formation: ≤ 5 % Off-target editing: 1-15%, rAPOBEC1-32aa linker-SaKKH-dCas9(A840H) nickase-9aa linker-UGI-9aa linker-UGI, Gam- rAPOBEC1-32aa linker-dCas9(A840H) nickase-9aa linker-UGI-9aa linker-UGI, Apparent editing efficiency: ~50% (in vivo); Indel formation: ≤ 1.5 % Off-target editing: 1-15%, rAPOBEC1-32aa linker-xCas9(A840H) nickase-9aa linker-UGI-9aa linker-UGI. Electroporation involves pulsing cells with high-voltage currents that create transient nanometre-size pores in the cell membrane to facilitate the delivery of base editor to cells. Therefore, the ADAR deaminase domain (ADARDD) can be recruited into the target RNA, which relies on the Watson-Crick base pairing between the antisense RNA and the target transcript. Help. Clone the gRNA into the gRNA expression vector compatible for your system. 2800 mAh (Li-Polymer) BLU Grand 5.5 HD II. For instance, YE1-BE3, YE2-BE3, EE-BE3, and YEE-BE3 are modified versions of BE3 with narrower active windows, but still show stable activity of base editing compared to regular BE3. BE3 nicks the nonedited DNA strand firstly, then converts G:U to A:U by activating cellular mismatch repair and finally converts A:U to A:T permanently during DNA replication and repair [ 15 ] (Figure 1 (a)). Hence, decreasing the ability of APOBEC1 binding to ssDNA or the high levels of UGI may be good choices to reduce SNVs [97]. The study of Xie’s group also showed that CBEs could induce C to T conversions at multiple sites in pig embryos simultaneously, and the mutation efficiency approximated 40~50% [67]. The ADAR can mediate endogenous conversion of adenosine to inosine via hydrolytic deamination. Dawn's Healthy Habits. After oral administration, peak blood levels were achieved after 15 or 30 minutes, and also declined triphasically with half-lives similar to what had been estimated from intravenous administration (0.32 +/ … Lifeplus is an international referral marketing company offering high quality nutritional supplements & organic skin care. Electroporation and lipofection are the primary methods used in vitro. All the studies demonstrate that the base editor can correct pathogenic gene mutations and have great prospect in gene therapy. CRISPR/Cas9 protein-RNA complexes were recruited to target DNA sequence via base pairing with a specified single guide RNA (sgRNA) and natively create a double strand breaks (DSBs), triggering cellular DNA repair by nonhomologous end joining (NHEJ) or homology-directed repair (HDR) to achieve genome editing eventually [7, 8]. Schematic of RNA editing by dCas13b-ADAR. Be3 Master Cleanse. Their study showed that the off-target single-nucleotide variants (SNVs) were rare in embryos of either CRISPR/Cas9 or ABEs, and the frequency close to the natural mutation rate. 4-20-2 Fuda Chofu-Shi, Tokyo 182-0024 Japan Tel : +81 42 440 3440 FAX : +81 42 440 3450 Email : autoparts@beforward.jp. Then, the deoxyadenosine deaminase domain catalyzes the conversion of adenine (A) to inosine (I). The Bar Plus is the ideal combination of stunning design and worry-free durability. 2600 mAh (Li-Polymer) BLU Grand XL. These studies mentioned all prove that base editor can be applied to generate mammal’s models, which could mimic the mutations associated with human disease and could be used to guide the treatment of disease to some extent. This work was supported by the National Key Research and Development Program (2016YFA0101401). Camera. While analyzing these data, we noticed that the product purities of CDA1-BE3 and AID-BE3 were typically higher than those of BE3 at those sites for which CDA1-BE3 and AID-BE3 edited more C’s than BE3 ().For example, at the HEK4 locus, BE3 efficiently edits only a single C (the C not preceded by a G), but both CDA1-BE3 and AID-BE3 edit three C’s (fig. Along with the flexibility and efficiency, a base editor has been widely used in many fields. We would like to show you a description here but the site won’t allow us. This Device: 48 MP. Depending on rapid improvement and optimization of gene editing technology, the prospect of base editor is immeasurable. Fujitsu Arrows Be3 F-02L is also known as Fujitsu F-02L. Besides, the team of Tan obtained two high-precision base editors that BE3-PAPAPAP mainly edits within an activity window from −14 to −16, and base editors with CDA1 truncations mainly edit at position −18 [25, 26]. Schematic of prime editor works in target DNA. At present, there have many prominent cases of base editor used in gene therapy for genetic disease (Table 2). ²Minimum of 10 secs for 256/128GB models; minimum of 14 secs for 64/32GB models (tested with combination of Asus Z370-G, Intel i7-8700K@3.70GHz, 8GB DDR4 and Windows 10 Enterprise 64bit). East, A. Cheng, S. Lin, E. Ma, and J. Doudna, “RNA-programmed genome editing in human cells,”, L. A. Gilbert, M. H. Larson, L. Morsut et al., “CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes,”, L. S. Qi, M. H. Larson, L. A. Gilbert et al., “Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression,”, D. J. Burgess, “Translational genetics: CRISPR therapies - making the grade not the cut,”, D. Bikard, W. Jiang, P. Samai, A. Hochschild, F. Zhang, and L. A. Marraffini, “Programmable repression and activation of bacterial gene expression using an engineered CRISPR-Cas system,”, S. Konermann, M. D. Brigham, A. E. Trevino et al., “Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex,”, F. A. Although base editor can help us to convert bases easily, there are still some problems needed to be addressed. Kotak Mahindra Life Insurance Company Ltd. is only the name of the Insurance Company and Kotak Single Invest Plus is only the name of the unit linked life insurance contract and does not in any way indicate the quality of the contract, its future prospects or returns. To further increase the editing efficiency of the base editor (CBE and ABE), Koblan et al. Zhou and coworkers also demonstrated that BE3 and ABE7.10 produced thousands of off-target in RNA level [102]. Nanoparticle is another alternative way to deliver base editor via endocytosis and micropinocytosis. Eventually, A:U is converted to A:T during DNA replication or repair. Up to now, there are several base editors’ variants have been developed. In 2017, Huang’s team reported the efficient correction of HBB (28 A>G) mutation in human primary cells and human embryos by BE3 or BE3’s variants with corresponding sgRNA [50]. Improved DNA specificity; 16-70% editing efficiency in human cells Increased number of SNPs in ClinVar  database it can target (~71%). Europe PMC is a service of the Europe PMC Funders' Group, in partnership with the European Bioinformatics Institute Opens a new window; and in cooperation with the National Center for Biotechnology Information Opens a new window at the U.S. National Library of Medicine (NCBI/NLM) Opens a new window.It includes content provided to the PMC International archive Opens a new … Using a base editor to generate monogenic disease models and correct pathogenic point mutations is a breakthrough technology for exploration and treatment of human diseases. Four general methods for delivery are electroporation, lipofection, viral vectors, and nanoparticles. Moreover, two papers in nature verified that base editor could induce off-target in RNA. Yang and coworkers developed the Genome-wide Off-target analysis by Two-cell embryos Injection (GOTI) to detect off-target mutations. Moreover, in order to treat genetic disorders which were caused by multiletter mutations, such as Tay-Sachs disease caused by an insertion of four DNA letters into the HEXA gene [33], Anzalone et al. So, the result indicated that the APOBEC1 or UGI elements maybe responsible for the substantial off-target, because, in the natural state, APOBEC1 can bind single-stranded DNA (ssDNA) [93], and UGI can increase the spontaneous mutation rate [94, 95]. Di Noia and M. S. Neuberger, “Altering the pathway of immunoglobulin hypermutation by inhibiting uracil-DNA glycosylase,”, H. A. Rees and D. R. Liu, “Base editing: precision chemistry on the genome and transcriptome of living cells,”, M. R. Willmann, “Base editors and off-targeting: the deaminase matters,”, J. L. Doman, A. Raguram, G. A. Newby, and D. R. Liu, “Evaluation and minimization of Cas9-independent off-target DNA editing by cytosine base editors,”, M. Bratovič, I. Fonfara, K. Chylinski et al., “Bridge helix arginines play a critical role in Cas9 sensitivity to mismatches,”, H. S. Kim, Y. K. Jeong, J. K. Hur, J. S. Kim, and S. Bae, “Adenine base editors catalyze cytosine conversions in human cells,”, J. Grünewald, R. Zhou, S. P. Garcia et al., “Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors,”, C. Zhou, Y. Even the only curative therapy, bone marrow transplantation, is also limited by the antigen compatibility of human leukocyte. There is no doubt that the base editor provides a powerful strategy for exploring the mechanisms and treating monogenetic disease, which have the potential to broadly impact the biomedicine. Specifications Display Camera CPU Battery SAR. Join Facebook to connect with Titus Pinto and others you may know. Before 2016, researchers delivered CRIPSR/Cas9 with a donor DNA template to achieve gene correction. A3Bctd-VHM-BE3 and A3Bctd-KKR-BE3 also produced fewer multiple C-to-T edits and more single and double C-to-T edits than A3Bctd-BE3 ... Wizard Plus midipreps: Promega: CAT#A7640: 2 × Rapid Taq Master Mix: Vazyme Biotech co: CAT#P222-03: DNA Quick Plant System: Tiangen Biotech: CAT#DP321-03 : TransStart FastPfu Fly DNA Polymerase: TransGen Biotech: CAT#AP231 … For example, transcriptional repressors or activators were fused into catalytically inactivated Cas9 (dCas9) to achieve gene repression or activation [9–13]. 2012;109:E2579-86, Apparent editing efficiency: 44% (in vitro), 0.8-7.7% (in vivo) Indel formation: ≤ 0.1%, Apparent editing efficiency: 20% (in vivo) Indel formation: ≤ 0.1%, Apparent editing efficiency: 20-30% (in vitro) 15-75% (in vivo). Lipofection reagent wraps plasmid vector DNA, forming DNA-lipid complex which could be absorbed via endocytosis of cell membrane, but the toxicity can cause massive cell death. The BE3 team has the ability to plan and manage task orders on environmental projects nationwide including: ... Cost-plus fee – a cost plus fee contract is the best contract agreement for contractors. Samsung's leadership in flash memory makes the Bar Plus a trustworthy drive to store your valuable data. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. BE3: SpCas9 nickase (D10A) is linked to rat cytidine deaminase (rAPOBEC1) (pink) through the N terminus, and to uracil glycosylase inhibitor (UGI) (orange) at the C terminus. B. Kim, A. C. Komor, J. M. Levy, M. S. Packer, K. T. Zhao, and D. R. Liu, “Increasing the genome-targeting scope and precision of base editing with engineered Cas9-cytidine deaminase fusions,”, J. Tan, F. Zhang, D. Karcher, and R. Bock, “Engineering of high-precision base editors for site-specific single nucleotide replacement,”, J. Tan, F. Zhang, D. Karcher, and R. Bock, “Expanding the genome-targeting scope and the site selectivity of high-precision base editors,”, W. Jiang, S. Feng, S. Huang et al., “BE-PLUS: a new base editing tool with broadened editing window and enhanced fidelity,”, J. H. Hu, S. M. Miller, M. H. Geurts et al., “Evolved Cas9 variants with broad PAM compatibility and high DNA specificity,”, X. Li, Y. Wang, Y. Liu et al., “Base editing with a Cpf1-cytidine deaminase fusion,”, J. M. Gehrke, O. Cervantes, M. K. Clement et al., “An APOBEC3A-Cas9 base editor with minimized bystander and off-target activities,”, X. Wang, J. Li, Y. Wang et al., “Efficient base editing in methylated regions with a human APOBEC3A-Cas9 fusion,”, M. F. Richter, K. T. Zhao, E. Eton et al., “Phage-assisted evolution of an adenine base editor with improved Cas domain compatibility and activity,”, H. Ledford, “Super-precise new CRISPR tool could tackle a plethora of genetic diseases,”, A. V. Anzalone, P. B. Randolph, J. R. Davis et al., “Search-and-replace genome editing without double-strand breaks or donor DNA,”, K. Nishikura, “Functions and regulation of RNA editing by ADAR deaminases,”, M. H. Tan, Q. Li, R. Shanmugam et al., “Dynamic landscape and regulation of RNA editing in mammals,”, M. F. Montiel-Gonzalez, I. Vallecillo-Viejo, G. A. Yudowski, and J. J. C. Rosenthal, “Correction of mutations within the cystic fibrosis transmembrane conductance regulator by site-directed RNA editing,”, M. F. Montiel-Gonzalez, I. C. Vallecillo-Viejo, and J. J. Rosenthal, “An efficient system for selectively altering genetic information within mRNAs,”, M. Fukuda, H. Umeno, K. Nose, A. Nishitarumizu, R. Noguchi, and H. Nakagawa, “Construction of a guide-RNA for site-directed RNA mutagenesis utilising intracellular A-to-I RNA editing,”, J. Wettengel, P. Reautschnig, S. Geisler, P. J. Kahle, and T. Stafforst, “Harnessing human ADAR2 for RNA repair - recoding a PINK1 mutation rescues mitophagy,”, P. Vogel and T. Stafforst, “Site-directed RNA editing with antagomir deaminases--a tool to study protein and RNA function,”, P. Vogel, M. Moschref, Q. Li et al., “Efficient and precise editing of endogenous transcripts with SNAP-tagged ADARs,”, O. O. Abudayyeh, J. S. Gootenberg, S. Konermann et al., “C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector,”, S. Shmakov, O. O. Abudayyeh, K. S. Makarova et al., “Discovery and functional characterization of diverse class 2 CRISPR-Cas systems,”, S. Shmakov, A. Smargon, D. Scott et al., “Diversity and evolution of class 2 CRISPR-Cas systems,”, D. B. T. Cox, J. S. Gootenberg, O. O. Abudayyeh et al., “RNA editing with CRISPR-Cas13,”, O. O. Abudayyeh, J. S. Gootenberg, B. Franklin et al., “A cytosine deaminase for programmable single-base RNA editing,”, L. Qu, Z. Yi, S. Zhu et al., “Programmable RNA editing by recruiting endogenous ADAR using engineered RNAs,”, Y. Zong, Y. Wang, C. Li et al., “Precise base editing in rice, wheat and maize with a Cas9-cytidine deaminase fusion,”, P. Liang, C. Ding, H. Sun et al., “Correction of, P. Chatterjee, N. Jakimo, and J. M. Jacobson, “Minimal PAM specificity of a highly similar SpCas9 ortholog,”.