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ADAR-Mediated RNA Editing and Its Therapeutic Potentials

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Epitranscriptomics

Part of the book series: RNA Technologies ((RNATECHN,volume 12))

Abstract

Adenosine-to-inosine (A-to-I) RNA editing mediated by the ADAR (adenosine deaminase acting on RNA) protein family is the primary type of epitranscriptomic modification known to occur in mammal cells. Recently, several technologies have been developed to re-target this RNA modification to desired locations within specific transcripts. This possibility opened a scenario in which targeted RNA-base editing tools can be used as therapeutic strategies to correct mutations at the RNA level. The chapter will go into detail about the therapeutic potentials of these different RNA base-editing technologies, after providing a brief overview of the roles and functions of ADAR family members. The chapter aims to review the recent advancements of targeted RNA-base editing methodologies and their translation to therapeutic settings. We will discuss strategies leveraging exogenous and endogenous ADAR to create a wholesome perspective on the potential of this molecular mechanism as a tool to correct disease-causing G-to-A point mutations. In this context, clinically relevant approaches and their potential future applications, as well as their currently challenging limitations, will be evaluated.

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Abbreviations

A:

Adenosine

A1AT:

α1-antitrypsin

AAV:

Adeno-associated virus

AAV8:

Adeno-associated virus vector 8

ADAR:

Adenosine deaminase acting on RNA

ADAR2DD:

Deamination domain of ADAR2

ADAR2E488Q:

Hyperactive ADAR2 mutant carrying the E488Q mutation

ADAT:

Adenosine deaminase acting on tRNAs

adRNA or AD-gRNA:

ADAR guiding RNA

adV:

Adenovirus

ALS:

Amyotrophic lateral sclerosis

arRNA:

ADAR recruiting RNA

ASOs:

Antisense oligonucleotides

A-to-C:

Adenosine to cytosine

A-to-I:

Adenosine to inosine

BG:

O6-benzylguanine

C:

Cytosine

CDA:

Cytidine deaminase acting on mononucleotides

CFTR:

Cystic fibrosis transmembrane conductance regulator

CIRTS:

CRISPR-Cas-inspired RNA targeting system

CNS:

Central nervous system

dCas13b:

Catalytically inactive mutant of PspCas13b protein

DMD:

Duchenne muscular dystrophy

dsRBD:

Double-stranded RNA-binding domain

dsRBM:

Double-stranded RNA-binding motif

dsRNA:

Double-stranded RNA

eCFP:

Enhanced cyan fluorescent protein

eGFP:

Enhanced green fluorescent protein

EONs:

Editing oligonucleotides

G:

Guanosine

GluR2:

Glutamate ionotropic receptor

gRNA:

Guide RNA

G-to-A:

Guanosine to adenosine

HEK:

Human embryonic kidney

HeLa cells:

Henrietta Lacks cervical cancer cells

HEPN:

Higher-eukaryotes and prokaryotes nucleotide binding domain

I:

Inosine

IDUA:

α-L-iduronidase

IFN:

Interferon

IFN-I type :

Interferon type I

irCLASH:

Infrared-dye-conjugated and biotinylated ligation adapter-based CLASH protocol (Crosslinking, Ligation And Sequencing of Hybrids)

ISGs:

Interferon stimulated genes

IV:

Intravenous

IVT:

Intravitreal

LEAPER:

Leveraging endogenous ADAR for programmable editing of RNA

LINEs:

Long interspersed elements

MAVS:

Mitochondrial antiviral signalling protein

MCP:

MS2 coat protein

MDA5:

Melanoma differentiation-associated protein 5

MECP2:

Methyl CpG binding protein 2

MEF:

Mouse embryonic fibroblasts

MPS I:

Mucopolysaccharidosis type I

NES:

Nuclear export signal

NLS:

Nuclear localisation signal

OTC:

Ornithine transcarbamylase

PKR:

Protein kinase R

PRRs:

Pattern recognition receptors

Q/R site:

Glutamine (Q) to arginine (R) site

R/G motif:

Arginine (R) to glycine (G) motif

REPAIR:

RNA Editing for Programmable A to I Replacement

RESCUE:

RNA Editing for Specific C-to-U Exchange

RESTORE:

Recruiting Endogenous ADAR to Specific Transcripts for Oligonucleotide-mediated RNA Editing

RIG-I:

Retinoid acid-inducible gene I

RLR:

RIG-I like receptor

RTT:

Rett syndrome

ssRNA:

Single-stranded RNA

TALENs:

Transcription activator-like effector nucleases

tRNA:

Transfer RNA

U:

Uracil

UTRs:

Untranslated regions

ZFNs:

Zinc finger nucleases

λN:

λ-phage N protein

References

  • Aalto A (2018) Axiomer technology–Therapeutic oligonucleotides for directing site-specific A-to-I editing by endogenous ADAR enzymes. https://www.proqr.com/files/2020-08/Axiomer-technology-TIDES-2018.pdf

  • Abudayyeh OO, Gootenberg JS, Franklin B et al (2019) A cytosine deaminase for programmable single-base RNA editing. Science 365:382–386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Abudayyeh OO, Gootenberg JS, Konermann S et al (2016) C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector. In: Science 353(6299):aaf5573

    Google Scholar 

  • Bajad P, Jantsch MF, Keegan L et al (2017) A to I editing in disease is not fake news. RNA Biol 14:1223–1231

    Article  PubMed  PubMed Central  Google Scholar 

  • Basilio C, Wahba AJ, Lengyel P et al (1962) Synthetic polynucleotides and the amino acid code. V. Proc Natl Acad Sci U S A 48:613–616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bass BL, Nishikura K, Keller W et al (1997) A standardized nomenclature for adenosine deaminases that act on RNA. RNA 3:947–949

    CAS  PubMed  PubMed Central  Google Scholar 

  • Benne R, Van Den Burg J, Brakenhoff JPJ et al (1986) Major transcript of the frameshifted coxll gene from trypanosome mitochondria contains four nucleotides that are not encoded in the DNA. Cell 46:819–826

    Article  CAS  PubMed  Google Scholar 

  • Blakney AK, McKay PF, Yus BI et al (2019) Inside out: optimization of lipid nanoparticle formulations for exterior complexation and in vivo delivery of saRNA. Gene Ther 26:363–372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Borden EC (2019) Interferons α and β in cancer: therapeutic opportunities from new insights. Nat Rev Drug Discov 18:219–234

    Article  CAS  PubMed  Google Scholar 

  • Charlesworth CT, Deshpande PS, Dever DP et al (2019) Identification of preexisting adaptive immunity to Cas9 proteins in humans. Nat Med 25:249–254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen CX, Cho DS, Wang Q et al (2000) A third member of the RNA-specific adenosine deaminase gene binding domains. RNA 6:755–767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chhabra ES, Moore N, Furcht C et al (2015) Evaluation of enhanced in vitro plasma stability of a novel long acting recombinant FVIIIFc-VWF-XTEN fusion protein. Blood 126:2279–2279

    Article  Google Scholar 

  • Cho SW, Kim S, Kim Y et al (2014) Analysis of off-target effects of CRISPR/Cas-derived RNA-guided endonucleases and nickases. Genome Res 24:132–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cho DSC, Yang W, Lee JT et al (2003) Requirement of dimerization for RNA editing activity of adenosine deaminases acting on RNA. J Biol Chem 278:17093–17102

    Article  CAS  PubMed  Google Scholar 

  • Chung H, Calis JJA, Wu X et al (2018) Human ADAR1 prevents endogenous RNA from triggering translational shutdown article human ADAR1 prevents endogenous RNA from triggering translational shutdown. Cell 172:811–824.e14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cox DBT, Gootenberg JS, Abudayyeh OO et al (2017) RNA editing with CRISPR-Cas13. Science (80-) 358:1019–1027

    Article  CAS  Google Scholar 

  • Crudele JM, Chamberlain JS (2018) Cas9 immunity creates challenges for CRISPR gene editing therapies. Nat Commun 9:9–11

    Article  CAS  Google Scholar 

  • East-Seletsky A, O’Connell MR, Knight SC et al (2016) Two distinct RNase activities of CRISPR-C2c2 enable guide-RNA processing and RNA detection. Nature 538:270–273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Egebjerg J, Heinemann SF (1993) Ca2+ permeability of unedited and edited versions of the kainate selective glutamate receptor GluR6. Proc Natl Acad Sci U S A 90:755–759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fu Y, Foden JA, Khayter C et al (2013) High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nat Biotechnol 31:822–826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fukuda M, Kurihara K, Tanaka Y et al (2012) A strategy for developing a hammerhead ribozyme for selective RNA cleavage depending on substitutional RNA editing. RNA 18:1735–1744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fukuda M, Umeno H, Nose K et al (2017) Construction of a guide-RNA for site-directed RNA mutagenesis utilising intracellular A-to-I RNA editing. Sci Rep 7:8–19

    Article  CAS  Google Scholar 

  • Gabriel R, Lombardo A, Arens A et al (2011) An unbiased genome-wide analysis of zinc-finger nuclease specificity. Nat Biotechnol 29:816–823

    Article  CAS  PubMed  Google Scholar 

  • Gallo A, Vukic D, Michalík D et al (2017) ADAR RNA editing in human disease; more to it than meets the I. Hum Genet 136:1265–1278

    Article  CAS  PubMed  Google Scholar 

  • Gaudelli NM, Komor AC, Rees HA et al (2017) Programmable base editing of a•T to G•C in genomic DNA without DNA cleavage. Nature 551:464–471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gerber AP, Keller W (2001) RNA editing by base deamination: more enzymes, more targets, new mysteries. Trends Biochem Sci 26:376–384

    Article  CAS  PubMed  Google Scholar 

  • Hacein-Bey-Abina S, Garrigue A, Wang GP et al (2008) Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1 find the latest version : insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest 118:3132–3142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Helwak A, Tollervey D (2014) Mapping the miRNA interactome by cross-linking ligation and sequencing of hybrids (CLASH). Nat Protoc 9:711–728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herbert A, Rich A (2001) The role of binding domains for dsRNA and Z-DNA in the in vivo editing of minimal substrates by ADAR1. Proc Natl Acad Sci U S A 98:12132–12137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Higuchi M, Maas S, Single FN et al (2000) Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2. Nature 406:78–81

    Article  CAS  PubMed  Google Scholar 

  • Katrekar D, Chen G, Meluzzi D et al (2019) In vivo RNA editing of point mutations via RNA-guided adenosine deaminases. Nat Methods 16:239–242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keegan LP, Gallo A, O’Connell MA (2001) The many roles of an RNA editor. Nat Rev Genet 2:869–878

    Article  CAS  PubMed  Google Scholar 

  • Keppler A, Gendreizig S, Gronemeyer T et al (2003) A general method for the covalent labeling of fusion proteins with small molecules in vivo. Nat Biotechnol 21:86–89

    Article  CAS  PubMed  Google Scholar 

  • Kim S, Lee MJ, Kim H et al (2011) Preassembled zinc-finger arrays for rapid construction of ZFNs. Nat Methods 8:7

    Article  CAS  PubMed  Google Scholar 

  • Kuttan A, Bass BL (2012) Mechanistic insights into editing-site specificity of ADARs. Proc Natl Acad Sci U S A 109:E3295–E3304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lamers MM, van den Hoogen BG, Haagmans BL (2019) ADAR1: “editor-in-chief” of cytoplasmic innate immunity. Front Immunol 10:1763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lehmann KA, Bass BL (1999) The importance of internal loops within RNA substrates of ADAR1. J Mol Biol 291:1–13

    Article  CAS  PubMed  Google Scholar 

  • Li H, Yang Y, Hong W et al (2020) Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects. Signal Transduct Target Ther 5:1

    Article  PubMed  PubMed Central  Google Scholar 

  • Liddicoat BJ, Piskol R, Chalk AM et al (2015) RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself. Science 349:1115–1120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lundstrom K (2018) Viral vectors in gene therapy. Diseases 6(2):42

    Article  PubMed Central  CAS  Google Scholar 

  • Maas S, Gommans WM (2009) Identification of a selective nuclear import signal in adenosine deaminases acting on RNA. Nucleic Acids Res 37:5822–5829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maas S, Patt S, Schrey M et al (2001) Underediting of glutamate receptor Glur-B mRNA in malignant gliomas. Proc Natl Acad Sci U S A 98:14687–14692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Miller JC, Tan S, Qiao G et al (2011) A TALE nuclease architecture for efficient genome editing. Nat Biotechnol 29:143–150

    Article  CAS  PubMed  Google Scholar 

  • Mladenova D, Barry G, Konen LM et al (2018) Adar3 is involved in learning and memory in mice. Front Neurosci 12:1–17

    Article  Google Scholar 

  • Montiel-Gonźalez MF, Vallecillo-Viejo IC, Rosenthal JJC (2016) An efficient system for selectively altering genetic information within mRNAs. Nucleic Acids Res 44:1–12

    CAS  Google Scholar 

  • Montiel-Gonzalez MF, Vallecillo-Viejo I, Yudowski GA et al (2013) Correction of mutations within the cystic fibrosis transmembrane conductance regulator by site-directed RNA editing. Proc Natl Acad Sci U S A 110:18285–18290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morrison C (2018) Alnylam prepares to land first RNAi drug approval. Nat Rev Drug Discov 17:156–157

    Article  CAS  PubMed  Google Scholar 

  • Mout R, Ray M, Lee YW et al (2017) In vivo delivery of CRISPR/Cas9 for therapeutic gene editing: Progress and challenges. Bioconjug Chem 28:880–884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nishikura K (2010) Funtions and regulation of RNA editing by ADAR deaminases. Annu Rev Biochem 79:321–349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nishikura K (2016) A-to-I editing of coding and non-coding RNAs by ADARs. Nat Rev Mol Cell Biol 17:83–96

    Article  CAS  PubMed  Google Scholar 

  • Nóbrega C, Mendonça L, Matos CA (2020) Non-viral vectors for gene therapy. In: A handbook of gene and Cell therapy. Springer International Publishing, Cham, pp 23–37

    Chapter  Google Scholar 

  • Oakes E, Anderson A, Cohen-Gadol A et al (2017) Adenosine deaminase that acts on RNA 3 (adar3) binding to glutamate receptor subunit B pre-mRNA inhibits RNA editing in glioblastoma. J Biol Chem 292:4326–4335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pattanayak V, Lin S, Guilinger JP et al (2013) High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity. Nat Biotechnol 31:839–843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patterson JB, Samuel CE (1995) Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells: evidence for two forms of the deaminase. Mol Cell Biol 15:5376–5388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pestal K, Funk CC, Snyder JM et al (2015) Isoforms of the RNA editing enzyme ADAR1 independently control nucleic acid sensor MDA5-driven autoimmunity and multi-organ development. Immunity 43:933–944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • ProQR Therapeutics (2020) Axiomer technology–Therapeutic oligonucleotides for directing site-specific A-to-I editing by endogenous ADAR enzymes. https://www.proqr.com/files/2020-08/Axiomer public overview 2020.pdf

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rice GI, Kasher PR, Forte GMA et al (2012) Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature. Nat Genet 44:1243–1248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roberts TC, Langer R, Wood MJA (2020) Advances in oligonucleotide drug delivery. Nat Rev Drug Discov 19(10):673–694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rueter SM, Dawson TR, Emeson RB (1999) Regulation of alternative splicing by RNA editing. Nature 399:75–80

    Article  CAS  PubMed  Google Scholar 

  • Samuel CE (2019) Adenosine deaminase acting on RNA (ADAR1), a suppressor of double-stranded RNA–triggered innate immune responses. J Biol Chem 294:1710–1720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Savva YA, Rieder LE, Reenan RA (2012) The ADAR protein family. Genome Biol 13:252

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Schneider MF, Wettengel J, Hoffmann PC et al (2014) Optimal guideRNAs for re-directing deaminase activity of hADAR1 and hADAR2 in trans. Nucleic Acids Res 42:1–9

    Article  CAS  Google Scholar 

  • Seeburg PH, Higuchi M, Sprengel R (1998) RNA editing of brain glutamate receptor channels: mechanism and physiology. Brain Res Rev 26:217–229

    Article  CAS  PubMed  Google Scholar 

  • Sinnamon JR, Kim SY, Corson GM et al (2017) Site-directed RNA repair of endogenous Mecp2 RNA in neurons. Proc Natl Acad Sci U S A 114:E9395–E9402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sinnamon JR, Kim SY, Fisk JR et al (2020) In vivo repair of a protein underlying a neurological disorder by programmable RNA editing. Cell Rep 32:107878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sommer B, Köhler M, Sprengel R et al (1991) RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell 67:11–19

    Article  CAS  PubMed  Google Scholar 

  • Song Y, Yang W, Fu Q et al (2020) irCLASH reveals RNA substrates recognized by human ADARs. Nat Struct Mol Biol 27:351–362

    Article  CAS  PubMed  Google Scholar 

  • Stafforst T, Schneider MF (2012) An RNA-deaminase conjugate selectively repairs point mutations. Angew Chemie–Int Ed 51:11166–11169

    Article  CAS  Google Scholar 

  • Stefl R, Oberstrass FC, Hood JL et al (2010) The solution structure of the ADAR2 dsRBM-RNA complex reveals a sequence-specific read out of the RNA minor groove. Cell 143:225–237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strehblow A, Hallegger M, Jantsch MF (2002) Nucleocytoplasmic distribution of human RNA- editing enzyme ADAR1 is modulated by double- stranded RNA-binding domains, a leucine-rich export signal, and a putative dimerization domain. Mol Biol Cell 13:3822–3835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang R, Xu Z (2020) Gene therapy: a double-edged sword with great powers. Mol Cell Biochem 474:73–81

    Article  CAS  PubMed  Google Scholar 

  • Tohama T, Sakari M, Tsukahara T (2020) Development of a single construct system for site-directed rna editing using MS2-ADAR. Int J Mol Sci 21:1–11

    Article  CAS  Google Scholar 

  • Twomey EC, Yelshanskaya MV, Grassucci R et al (2017) Channel opening and gating mechanism in AMPA-subtype glutamate receptors. Nature 549:60–65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vallecillo-Viejo IC, Liscovitch-Brauer N, Montiel-Gonzalez MF et al (2018) Abundant off-target edits from site-directed RNA editing can be reduced by nuclear localization of the editing enzyme. RNA Biol 15:104–114

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vogel P, Schneider MF, Wettengel J et al (2014) Improving site-directed RNA editing in vitro and in cell culture by chemical modification of the guideRNA. Angew Chemie–Int Ed 53:6267–6271

    Article  CAS  Google Scholar 

  • Vogel P, Stafforst T (2019) Critical review on engineering deaminases for site-directed RNA editing. Curr Opin Biotechnol 55:74–80

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Miyakoda M, Yang W et al (2004) Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene. J Biol Chem 279:4952–4961

    Article  CAS  PubMed  Google Scholar 

  • Wang F, Wang L, Zou X et al (2019) Advances in CRISPR-Cas systems for RNA targeting, tracking and editing. Biotechnol Adv 37:708–729

    Article  CAS  PubMed  Google Scholar 

  • Wang C, Zou J, Ma X et al (2017) Mechanisms and implications of ADAR-mediated RNA editing in cancer. Cancer Lett 411:27–34

    Article  CAS  PubMed  Google Scholar 

  • Ward SV, George CX, Welch MJ et al (2011) RNA editing enzyme adenosine deaminase is a restriction factor for controlling measles virus replication that also is required for embryogenesis. Proc Natl Acad Sci U S A 108:331–336

    Article  CAS  PubMed  Google Scholar 

  • Wettengel J, Reautschnig P, Geisler S et al (2017) Harnessing human ADAR2 for RNA repair–recoding a PINK1 mutation rescues mitophagy. Nucleic Acids Res 45:2797–2808

    CAS  PubMed  Google Scholar 

  • Wong SK, Sato S, Lazinski DW (2001) Substrate recognition by ADAR1 and ADAR2. RNA 7:846–858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woolf TM, Chase JM, Stinchcomb DT (1995) Toward the therapeutic editing of mutated RNA sequences. Proc Natl Acad Sci U S A 92:8298–8302

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu L-D, Öhman M (2019) ADAR1 editing and its role in cancer. Genes (Basel) 10(1):12

    Article  CAS  Google Scholar 

  • Zetche B, Volz SE, Zhang F (2015) A split-Cas9 architecture for inducible genome editing and transcription modulation. Nat Biotechnol 33:139–142

    Article  PubMed Central  CAS  Google Scholar 

  • Zhang XJ, He PP, Li M et al (2004) Seven novel mutations of the ADAR gene in Chinese families and sporadic patients with dyschromatosis symmetrica hereditaria (DSH). Hum Mutat 23:629–630

    Article  CAS  PubMed  Google Scholar 

  • Zhang XH, Tee LY, Wang XG et al (2015) Off-target effects in CRISPR/Cas9-mediated genome engineering. Mol Ther–Nucleic Acids 4:e264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author notes

  1. Beatrice Casati and Dimitra Stamkopoulou contributed equally to this work.

Authors and Affiliations

  1. Division of Immune Diversity, Program in Cancer Immunology, German Cancer Research Centre (DKFZ), Heidelberg, Germany

    Beatrice Casati, Dimitra Stamkopoulou, Rafail Nikolaos Tasakis & Riccardo Pecori

  2. Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany

    Beatrice Casati & Rafail Nikolaos Tasakis

  3. Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany

    Dimitra Stamkopoulou

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  1. Beatrice Casati
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  2. Dimitra Stamkopoulou
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  3. Rafail Nikolaos Tasakis
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  4. Riccardo Pecori
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Correspondence to Riccardo Pecori .

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Editors and Affiliations

  1. Nanobiomedical Center, Adam Mickiewicz University, Poznań, Poland

    Stefan Jurga

  2. Nanobiomedical Center of the Adam Mickiewicz University, Poznań and, Institute of Bioorganic Chemistry of the Polish Academy of Sciences, Poznań, Poland

    Jan Barciszewski

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Casati, B., Stamkopoulou, D., Tasakis, R.N., Pecori, R. (2021). ADAR-Mediated RNA Editing and Its Therapeutic Potentials. In: Jurga, S., Barciszewski, J. (eds) Epitranscriptomics. RNA Technologies, vol 12. Springer, Cham. https://doi.org/10.1007/978-3-030-71612-7_18

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