Abstract：
:Current base editors (BEs) catalyze only base transitions (C to T and A to G) and cannot produce base transversions. Here we present BEs that cause C-to-A transversions in Escherichia coli and C-to-G transversions in mammalian cells. These glycosylase base editors (GBEs) consist of a Cas9 nickase, a cytidine deaminase and a uracil-DNA glycosylase (Ung). Ung excises the U base created by the deaminase, forming an apurinic/apyrimidinic (AP) site that initiates the DNA repair process. In E. coli, we used activation-induced cytidine deaminase (AID) to construct AID-nCas9-Ung and found that it converts C to A with an average editing specificity of 93.8% ± 4.8% and editing efficiency of 87.2% ± 6.9%. For use in mammalian cells, we replaced AID with rat APOBEC1 (APOBEC-nCas9-Ung). We tested APOBEC-nCas9-Ung at 30 endogenous sites, and we observed C-to-G conversions with a high editing specificity at the sixth position of the protospacer between 29.7% and 92.2% and an editing efficiency between 5.3% and 53.0%. APOBEC-nCas9-Ung supplements the current adenine and cytidine BEs (ABE and CBE, respectively) and could be used to target G/C disease-causing mutations.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Zhao D,Li J,Li S,Xin X,Hu M,Price MA,Rosser SJ,Bi C,Zhang Xdoi
10.1038/s41587-020-0592-2subject
Has Abstractpub_date
2021-01-01 00:00:00pages
35-40issue
1eissn
1087-0156issn
1546-1696pii
10.1038/s41587-020-0592-2journal_volume
39pub_type
杂志文章abstract：:Peptide nucleic acids (PNAs) form stable and tight complexes with complementary DNA and/or RNA and would be promising antisense reagents if their cellular delivery could be improved. We show that a 21-mer PNA, complementary to the human galanin receptor type 1 mRNA, coupled to the cellular transporter peptides, transp...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt0998-857
更新日期：1998-09-01 00:00:00
abstract：:Of paramount importance for the development of cell therapies to treat diabetes is the production of sufficient numbers of pancreatic endocrine cells that function similarly to primary islets. We have developed a differentiation process that converts human embryonic stem (hES) cells to endocrine cells capable of synth...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt1259
更新日期：2006-11-01 00:00:00
abstract：:The excitement and controversy surrounding the potential role of human embryonic stem (ES) cells in transplantation therapy have often overshadowed their potentially more important use as a basic research tool for understanding the development and function of human tissues. Human ES cells can proliferate without a kno...
journal_title：Nature biotechnology
pub_type：
doi：10.1038/nbt761
更新日期：2002-12-01 00:00:00
abstract：:Current tools for targeted RNA editing rely on the delivery of exogenous proteins or chemically modified guide RNAs, which may lead to aberrant effector activity, delivery barrier or immunogenicity. Here, we present an approach, called leveraging endogenous ADAR for programmable editing of RNA (LEAPER), that employs s...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/s41587-019-0178-z
更新日期：2019-09-01 00:00:00
abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title：Nature biotechnology
pub_type： 杂志文章,已发布勘误
doi：10.1038/s41587-020-0457-8
更新日期：2020-03-01 00:00:00
abstract：:Vaccination with dendritic cells (DCs) pulsed with antigenic peptides derived from various tumor antigens has great, but as yet significantly unrealized, potential in cancer treatment. Here, we describe a strategy for prolonged presentation of an MHC class I-restricted self-peptide on DCs through linkage of it to a ce...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt0202-149
更新日期：2002-02-01 00:00:00
abstract：:We describe a simple technology used to cure an established metastatic disease. Intradermal injection of plasmid DNA encoding a transcriptionally targeted cytotoxic gene, along with hsp70, not only promoted tissue-specific, inflammatory killing of normal melanocytes, but also induced a CD8(+) T-cell-dependent, antigen...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt1007
更新日期：2004-09-01 00:00:00
abstract：:The ability to produce monoclonal antibodies (Mabs) in plants offers the opportunity for the development of an inexpensive method of mucosal immunoprotection against sexually transmitted diseases. To investigate the suitability of plant-expressed Mabs for vaginal preventive applications, we compared a humanized anti-h...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/4344
更新日期：1998-12-01 00:00:00
abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title：Nature biotechnology
pub_type： 已发布勘误
doi：10.1038/s41587-019-0320-y
更新日期：2019-12-01 00:00:00
abstract：:Live cell imaging is a powerful method to study protein dynamics at the cell surface, but conventional imaging probes are bulky, or interfere with protein function, or dissociate from proteins after internalization. Here, we report technology for covalent, specific tagging of cellular proteins with chemical probes. Th...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt1355
更新日期：2007-12-01 00:00:00
abstract：:Mass spectrometry-based quantitative proteomics has become an important component of biological and clinical research. Although such analyses typically assume that a protein's peptide fragments are observed with equal likelihood, only a few so-called 'proteotypic' peptides are repeatedly and consistently identified fo...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt1275
更新日期：2007-01-01 00:00:00
abstract：:Analyzing patent data from 1995-2005 show the increasing importance of patenting by small and medium-sized biotech companies. ...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt0606-643
更新日期：2006-06-01 00:00:00
abstract：:A broad-specificity delta 9 desaturase gene was cloned from the cyanobacterium Anacystis nidulans. The enzyme introduces a cis-double bond at the delta 9 position of both 16 and 18 carbon saturated fatty acids linked to many kinds of membrane lipids. The gene was stably introduced into tobacco plants under transcripti...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt0896-1003
更新日期：1996-08-01 00:00:00
abstract：:The biology of multicellular organisms is coordinated across multiple size scales, from the subnanoscale of molecules to the macroscale, tissue-wide interconnectivity of cell populations. Here we introduce a method for super-resolution imaging of the multiscale organization of intact tissues. The method, called magnif...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt.3641
更新日期：2016-09-01 00:00:00
abstract：:Current DNA methylation assays are limited in the flexibility and efficiency of characterizing a large number of genomic targets. We report a method to specifically capture an arbitrary subset of genomic targets for single-molecule bisulfite sequencing for digital quantification of DNA methylation at single-nucleotide...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt.1530
更新日期：2009-04-01 00:00:00
abstract：:Functional genomics and proteomics are identifying many potential drug targets for novel therapeutic proteins, and both rational and combinatorial protein engineering methods are available for creating drug candidates. A central challenge is the definition of the most appropriate design criteria, which will benefit cr...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt1064
更新日期：2005-02-01 00:00:00
abstract：:After nearly 40 years of development, oligonucleotide therapeutics are nearing meaningful clinical productivity. One of the key advantages of oligonucleotide drugs is that their delivery and potency are derived primarily from the chemical structure of the oligonucleotide whereas their target is defined by the base seq...
journal_title：Nature biotechnology
pub_type： 杂志文章,评审
doi：10.1038/nbt.3765
更新日期：2017-03-01 00:00:00
abstract：:Complex interactions among genetic components often result in variable systemic performance in designed multigene systems. Using the bacterial clustered regularly interspaced short palindromic repeat (CRISPR) pathway we develop a synthetic RNA-processing platform, and show that efficient and specific cleavage of precu...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt.2355
更新日期：2012-10-01 00:00:00
abstract：:Calcium (Ca(2+)) signals that are precisely modulated in space and time mediate a myriad of cellular processes, including contraction, excitation, growth, differentiation and apoptosis. However, study of Ca(2+) responses has been hampered by technological limitations of existing Ca(2+)-modulating tools. Here we presen...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt.3350
更新日期：2015-10-01 00:00:00
abstract：:Artificial transcription factors containing designer zinc-finger DNA-binding domains (DBDs) have been used to activate or repress expression of a growing number of endogenous genes. We have combined targeted zinc-finger DBD technology with a dimerizer-regulated gene expression system to permit the small-molecule contr...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt0702-729
更新日期：2002-07-01 00:00:00
abstract：:Efficient delivery of small interfering (si)RNA to specific cell populations in vivo remains a formidable challenge to its successful therapeutic application. We show that siRNA synthetically linked to a CpG oligonucleotide agonist of toll-like receptor (TLR)9 targets and silences genes in TLR9(+) myeloid cells and B ...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt.1564
更新日期：2009-10-01 00:00:00
abstract：:High-density short oligonucleotide microarrays have become a widely used tool for measuring gene expression on a large scale. However, details of the mechanism of binding on microarrays remain unclear. Short oligonucleotide probes currently synthesized on microarrays are often ineffective as a result of limited sequen...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt836
更新日期：2003-07-01 00:00:00
abstract：:Centromeric variation has been linked to cancer and infertility, but centromere sequences contain multiple tandem repeats and can only be assembled manually from long error-prone reads. Here we describe the centroFlye algorithm for centromere assembly using long error-prone reads, and apply it to assemble human centro...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/s41587-020-0582-4
更新日期：2020-11-01 00:00:00
abstract：:A human skin allograft injury model in immunodeficient mice, engrafted with human peripheral blood mononuclear cells from a different donor, has been used to test whether reagents that block human T cell CD2 interactions with its principal ligand, LFA-3 (CD58), can inhibit immune reactions in vivo. In this model, huma...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt0897-759
更新日期：1997-08-01 00:00:00
abstract：:A protocol was established for the introduction of DNA into embryogenic suspension-derived tissues of cassava via microparticle bombardment, for the selection of genetically transformed cells, and for the regeneration of fully transgenic plants from these cells. The plasmid DNA used for bombardment contained a gene en...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt0696-731
更新日期：1996-06-01 00:00:00
abstract：:Selectable marker genes are required to ensure the efficient genetic modification of crops. Economic incentives and safety concerns have prompted the development of several strategies (site-specific recombination, homologous recombination, transposition, and co-transformation) to eliminate these genes from the genome ...
journal_title：Nature biotechnology
pub_type： 杂志文章,评审
doi：10.1038/nbt0602-575
更新日期：2002-06-01 00:00:00
abstract：:A problem in analyzing microarray-based gene expression data is the separation of genes causally involved in a disease from innocent bystander genes, whose expression levels have been secondarily altered by primary changes elsewhere. To investigate this issue systematically in the context of a class of complex human d...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt965
更新日期：2004-05-01 00:00:00
abstract：:Methods to rapidly assess cell growth would be useful for many applications, including drug susceptibility testing, but current technologies have limited sensitivity or throughput. Here we present an approach to precisely and rapidly measure growth rates of many individual cells simultaneously. We flow cells in suspen...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt.3666
更新日期：2016-10-01 00:00:00
abstract：:We describe a new method of random mutagenesis that employs the addition of peptide tails with random sequences to the C-terminal of enzyme molecules. A mutant population of catalase I from Bacillus stearothermophilus prepared by this method has a diversity in thermostability and enzyme activity equal to that obtained...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/5232
更新日期：1999-01-01 00:00:00
abstract：:The construction of synthetic cell-cell communication networks can improve our quantitative understanding of naturally occurring signaling pathways and enhance our capabilities to engineer coordinated cellular behavior in cell populations. Towards accomplishing these goals in eukaryotes, we developed and analyzed two ...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt1162
更新日期：2005-12-01 00:00:00
