Front. Genome Ed. Frontiers in Genome Editing Front. Genome Ed. 2673-3439 Frontiers Media S.A. 10.3389/fgeed.2021.682171 Genome Editing Correction Corrigendum: Targeted Gene Delivery: Where to Land Pavani Giulia † Amendola Mario * INTEGRARE, UMR_S951, Genethon, Inserm, Univ Evry, Univ Paris-Saclay, Evry, France

Edited and reviewed by: Pietro Genovese, Boston Children's Hospital and Harvard Medical School, United States

 *Correspondence: Mario Amendola mamendola@genethon.fr

This article was submitted to Genome Editing in Blood Disorders, a section of the journal Frontiers in Genome Editing

†Present address: Giulia Pavani, The Children's Hospital of Philadelphia, Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Philadelphia, PA, United States

 17 05 2021 2021 3 682171 17 03 2021 06 04 2021 Copyright © 2021 Pavani and Amendola. 2021 Pavani and Amendola

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

 A Corrigendum on Targeted Gene Delivery: Where to Land by Pavani, G., and Amendola, M. (2021). Front. Genome Ed. 2:609650. doi: 10.3389/fgeed.2020.609650 genome editing gene therapy nuclease CRISPR targeted integration (TI) knock-in safe harbor homologous recombination (HR)

In the original article, there was a mistake in Table 1 as published. The references indicated in row B are wrong. The corrected Table 1 appears in the attached below.

(A–F) The advantages and disadvantages of different integration strategies.

Integration strategies Advantages Disadvantages References
A Endogenous locus Physiological transgene expression Corrects multiple mutations Gene-specific strategy Limited to gene body mutations Urnov et al., 2005; Lombardo et al., 2007; Li et al., 2011; Genovese et al., 2014; Voit et al., 2014; Dever et al., 2016; Hubbard et al., 2016; Schiroli et al., 2017; Sweeney et al., 2017; Kuo et al., 2018; Wang et al., 2019; Rai et al., 2020; Wang L. et al., 2020
B Superactive promoters (ALB, HBA) Accommodates different transgenes Supraphysiological expression Few integrations required Partial gene disruption Limited to non-cell autonomous disorders Extensive validation required Barzel et al., 2015; Sharma et al., 2015; Davidoff and Nathwani, 2016; Laoharawee et al., 2018; Chen et al., 2019; Conway et al., 2019; De Caneva et al., 2019; Ou et al., 2019, 2020; Zhang et al., 2019; Wang Q. et al., 2020
C Tolerant to integration (AAVS1, CCR5, Rosa26) Accommodates different transgenes Artificial promoters required Variable expression De Ravin et al., 2016; Diez et al., 2017; Stephens et al., 2018, 2019; Gomez-Ospina et al., 2019; Scharenberg et al., 2020
D Chromatin domains (NAD) Fine gene regulation Far from oncogenic genes No proof-of-principle in clinically relevant models Schenkwein et al., 2020
E Disease-modifier genes (CCR5, HBA) Improve therapeutic effect Lower therapeutic threshold Extensive validation required Limited to well-known diseases Voit et al., 2013; Wiebking et al., 2018
F Specificity Exchange (TCR, BCR) Improved CAR expression and potency Off-targets Translocations risk (for multiple edits) Eyquem et al., 2017; MacLeod et al., 2017; Greiner et al., 2019; Hartweger et al., 2019; Moffett et al., 2019; Voss et al., 2019

Scissors: nuclease; Solid arrows: promoters; Enh, enhancers; TAD, topologically associating; d, domain; Solid ovals: histone modifications; Solid squares: DNA modifications.

The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.

References Barzel A. Paulk N. K. Shi Y. Huang Y. Chu K. Zhang F. . (2015). Promoterless gene targeting without nucleases ameliorates haemophilia B in mice. Nature 517, 360–364. 10.1038/nature1386425363772 Chen H. Shi M. Gilam A. Zheng Q. Zhang Y. Afrikanova I. . (2019). Hemophilia A ameliorated in mice by CRISPR-based in vivo genome editing of human factor. Sci. Rep. 9:16838. 10.1038/s41598-019-53198-y31727959 Conway A. Mendel M. Kim K. McGovern K. Boyko A. Zhang L. . (2019). Non-viral delivery of zinc finger nuclease mRNA enables highly efficient in vivo genome editing of multiple therapeutic gene targets. Mol. Ther. 27, 866–877. 10.1016/j.ymthe.2019.03.00330902585 Davidoff A. M. Nathwani A. C. (2016). Genetic targeting of the albumin locus to treat Hemophilia. N. Engl. J. Med. 374, 1288–1290. 10.1056/NEJMcibr160034727028920 De Caneva A. Porro F. Bortolussi G. Sola R. Lisjak M. Barzel A. . (2019). Coupling AAV-mediated promoterless gene targeting to SaCas9 nuclease to efficiently correct liver metabolic diseases. JCI Insight. 5:128863. 10.1172/jci.insight.12886331211694 De Ravin S. S. Reik A. Liu P. Q. Li L. Wu X. Su L. . (2016). Targeted gene addition in human CD34(+) hematopoietic cells for correction of X-linked chronic granulomatous disease. Nat. Biotechnol. 34, 424–429. 10.1038/nbt.351326950749 Dever D. P. Bak R. O. Reinisch A. Camarena J. Washington G. Nicolas C. E. . (2016). CRISPR/Cas9 beta-globin gene targeting in human haematopoietic stem cells. Nature 539, 384–389. 10.1038/nature2013427820943 Diez B. Genovese P. Roman-Rodriguez F. J. Alvarez L. Schiroli G. Ugalde L. . (2017). Therapeutic gene editing in CD34(+) hematopoietic progenitors from Fanconi anemia patients. EMBO Mol. Med. 9, 1574–1588. 10.15252/emmm.20170754028899930 Eyquem J. Mansilla-Soto J. Giavridis T. van der Stegen S. J. Hamieh M. Cunanan K. M. . (2017). Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature 543, 113–117. 10.1038/nature2140528225754 Genovese P. Schiroli G. Escobar G. Tomaso T. D. Firrito C. Calabria A. . (2014). Targeted genome editing in human repopulating haematopoietic stem cells. Nature 510, 235–240. 10.1038/nature1342024870228 Gomez-Ospina N. Scharenberg S. G. Mostrel N. Bak R. O. Mantri S. Quadros R. M. . (2019). Human genome-edited hematopoietic stem cells phenotypically correct Mucopolysaccharidosis type. Nat. Commun. 10:4045. 10.1038/s41467-019-11962-831492863 Greiner V. Bou Puerto R. Liu S. Herbel C. Carmona E. M. Goldberg M. S. (2019). CRISPR-mediated editing of the B cell receptor in primary human B cells. iScience 12, 369–378. 10.1016/j.isci.2019.01.03230769282 Hartweger H. McGuire A. T. Horning M. Taylor J. J. Dosenovic P. Yost D. . (2019). HIV-specific humoral immune responses by CRISPR/Cas9-edited B cells. J. Exp. Med. 216, 1301–1310. 10.1084/jem.2019028730975893 Hubbard N. Hagin D. Sommer K. Song Y. Khan I. Clough C. . (2016). Targeted gene editing restores regulated CD40L function in X-linked hyper-IgM syndrome. Blood 127, 2513–2522. 10.1182/blood-2015-11-68323526903548 Kuo C. Y. Long J. D. Campo-Fernandez B. de Oliveira S. Cooper A. R. Romero Z. . (2018). Site-specific gene editing of human hematopoietic stem cells for X-linked hyper-IgM syndrome. Cell Rep. 23, 2606–2616. 10.1016/j.celrep.2018.04.10329847792 Laoharawee K. DeKelver R. C. Podetz-Pedersen K. M. Rohde M. Sproul S. Nguyen H. O. . (2018). Dose-dependent prevention of metabolic and neurologic disease in murine MPS II by ZFN-mediated in vivo genome editing. Mol. Ther. 26, 1127–1136. 10.1016/j.ymthe.2018.03.00229580682 Li H. Haurigot V. Doyon Y. Li T. Wong S. Y. Bhagwat A. S. . (2011). In vivo genome editing restores haemostasis in a mouse model of haemophilia. Nature 475, 217–221. 10.1038/nature1017721706032 Lombardo A. Genovese P. Beausejour C. M. Colleoni S. Lee Y. L. Kim K. A. . (2007). Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery. Nat. Biotechnol. 25, 1298–1306. 10.1038/nbt135317965707 MacLeod D. T. Antony J. Martin A. J. Moser R. J. Hekele A. Wetzel K. J. . (2017). Integration of a CD19 CAR into the TCR alpha chain locus streamlines production of allogeneic gene-edited CAR T cells. Mol. Ther. 25, 949–961. 10.1016/j.ymthe.2017.02.005 Moffett H. F. Harms C. K. Fitzpatrick K. S. Tooley M. R. Boonyaratanakornkit J. Taylor J. J. (2019). B cells engineered to express pathogen-specific antibodies protect against infection. Sci. Immunol. 4:aax0644. 10.1126/sciimmunol.aax0644 Ou L. DeKelver R. C. Rohde M. Tom S. Radeke R. St Martin S. J. . (2019). ZFN-mediated in vivo genome editing corrects murine hurler syndrome. Mol. Ther. 27, 178–187. 10.1016/j.ymthe.2018.10.018 Ou L. Przybilla M. J. Ahlat O. Kim S. Overn P. Jarnes J. . (2020). A highly efficacious PS gene editing system corrects metabolic and neurological complications of Mucopolysaccharidosis type I. Mol. Ther. 28, 1442–1454. 10.1016/j.ymthe.2020.03.018 Rai R. Romito M. Rivers E. Turchiano G. Blattner G. Vetharoy W. . (2020). Targeted gene correction of human hematopoietic stem cells for the treatment of Wiskott - Aldrich Syndrome. Nat. Commun. 11:4034. 10.1038/s41467-020-17626-2 Scharenberg S. G. Poletto E. Lucot K. L. Colella P. Sheikali A. Montine T. J. . (2020). Engineering monocyte/macrophage-specific glucocerebrosidase expression in human hematopoietic stem cells using genome editing. Nat. Commun. 11:3327. 10.1038/s41467-020-17148-x32820153 Schenkwein D. Afzal S. Nousiainen A. Schmidt M. Yla-Herttuala S. (2020). Efficient nuclease-directed integration of lentivirus vectors into the human ribosomal DNA locus. Mol. Ther. 28, 1858–1875. 10.1016/j.ymthe.2020.05.01932504545 Schiroli G. Ferrari S. Conway A. Jacob A. Capo V. Albano L. . (2017). Preclinical modeling highlights the therapeutic potential of hematopoietic stem cell gene editing for correction of SCID-X1. Sci. Transl. Med. 9:aan0820. 10.1126/scitranslmed.aan082029021165 Sharma R. Anguela X. M. Doyon Y. Wechsler T. DeKelver R. C. Sproul S. . (2015). In vivo genome editing of the albumin locus as a platform for protein replacement therapy. Blood 126, 1777–1784. 10.1182/blood-2014-12-61549226297739 Stephens C. J. Kashentseva E. Everett W. Kaliberova L. Curiel D. T. (2018). Targeted in vivo knock-in of human alpha-1-antitrypsin cDNA using adenoviral delivery of CRISPR/Cas9. Gene Ther. 25, 139–156. 10.1038/s41434-018-0003-129588497 Stephens C. J. Lauron E. J. Kashentseva E. Lu Z. H. Yokoyama W. M. Curiel D. T. (2019). Long-term correction of hemophilia B using adenoviral delivery of CRISPR/Cas9. J. Contr. Release. 298, 128–141. 10.1016/j.jconrel.2019.02.00930771412 Sweeney C. L. Zou J. Choi U. Merling R. K. Liu A. Bodansky A. . (2017). Targeted repair of CYBB in X-CGD iPSCs requires retention of intronic sequences for expression and functional correction. Mol. Ther. 25, 321–330. 10.1016/j.ymthe.2016.11.01228153086 Urnov F. D. Miller J. C. Lee Y. L. Beausejour C. M. Rock J. M. Augustus S. . (2005). Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 435, 646–651. 10.1038/nature0355615806097 Voit R. A. Hendel A. Pruett-Miller S. M. Porteus M. H. (2014). Nuclease-mediated gene editing by homologous recombination of the human globin locus. Nucl. Acids Res. 42, 1365–1378. 10.1093/nar/gkt94724157834 Voit R. A. McMahon M. A. Sawyer S. L. Porteus M. H. (2013). Generation of an HIV resistant T-cell line by targeted “stacking” of restriction factors. Mol. Ther. 21, 786–795. 10.1038/mt.2012.28423358186 Voss J. E. Gonzalez-Martin A. Andrabi R. Fuller R. P. Murrell B. McCoy L. E. . (2019). Reprogramming the antigen specificity of B cells using genome-editing technologies. Elife 8:42995. 10.7554/eLife.4299530648968 Wang L. Yang Y. Breton C. Bell P. Li M. Zhang J. . (2020). A mutation-independent CRISPR-Cas9-mediated gene targeting approach to treat a murine model of ornithine transcarbamylase deficiency. Sci. Adv. 6:eaax5701. 10.1126/sciadv.aax570132095520 Wang L. Yang Y. Breton C. A. White J. Zhang J. Che Y. . (2019). CRISPR/Cas9-mediated in vivo gene targeting corrects hemostasis in newborn and adult factor IX-knockout mice. Blood 133, 2745–2752. 10.1182/blood.201900079030975639 Wang Q. Zhong X. Li Q. Su J. Liu Y. Mo L. . (2020). CRISPR-Cas9-mediated in vivo gene integration at the albumin locus recovers hemostasis in neonatal and adult hemophilia B mice. Mol. Ther. Methods Clin. Dev. 18, 520–531. 10.1016/j.omtm.2020.06.02532775489 Wiebking V. Patterson J. O. Martin R. Chanda M. K. Lee C. M. Srifa W. . (2018). Metabolic engineering generates a transgene-free safety switch for cell therapy. Nat. Biotechnol 2020:6. 10.1038/s41587-020-0580-632661439 Zhang J. P. Cheng X. X. Zhao M. Li G. H. Xu J. Zhang F. . (2019). Curing hemophilia A by NHEJ-mediated ectopic F8 insertion in the mouse. Genome Biol. 20:276. 10.1186/s13059-019-1907-931843008