Gene editing studies for the treatment of AIDS

Author :  

Year-Number: 2020-1
Language : English
Konu : Genetics Engineering
Number of pages: 8-20
Mendeley EndNote Alıntı Yap

Abstract

Following after the fatal genetic diseases that were caused by single nucleotide polymorphisms (SNPs) and cancer, HIV/AIDS had always been one of the primary targets of cell and gene therapies due to lack of any proper satisfactory treatment. Earlier gene therapy approaches were mostly trials about introducing anti-HIV genes to cells, using various viral vectors. These viral vectors performed integrations of the desired anti-HIV genes, sometimes correctly while sometimes between random wrong sequences. However, with the increased precision of new gene editing technologies, including ZFNs and the latest CRISPR-mediated gene editing systems (Clustered Regularly Interspaced Short Palindromic Repeats) more successful therapies have begun to be administrated. As an important example of therapy, the trial of Timothy Ray Brown which was followed by the “London patient”, allowed the topic of gene editing techniques for treatment of HIV and AIDS to gain interest again.

Keywords

Abstract

Following after the fatal genetic diseases that were caused by single nucleotide polymorphisms (SNPs) and cancer, HIV/AIDS had always been one of the primary targets of cell and gene therapies due to lack of any proper satisfactory treatment. Earlier gene therapy approaches were mostly trials about introducing anti-HIV genes to cells, using various viral vectors. These viral vectors performed integrations of the desired anti-HIV genes, sometimes correctly while sometimes between random wrong sequences. However, with the increased precision of new gene editing technologies, including ZFNs and the latest CRISPR-mediated gene editing systems (Clustered Regularly Interspaced Short Palindromic Repeats) more successful therapies have begun to be administrated. As an important example of therapy, the trial of Timothy Ray Brown which was followed by the “London patient”, allowed the topic of gene editing techniques for treatment of HIV and AIDS to gain interest again.

Keywords


  • Afkhami S, Yao Y, Xing Z (2016). Methods and clinical

  • Afkhami S, Yao Y, Xing Z (2016). Methods and clinicaldevelopment of adenovirus-vectored vaccines against mucosalpathogens. Molecular Therapy-Methods & Clinical Development 3:16030

  • Allers K, Hütter G, Hofmann J, Loddenkemper C, Rieger K,Thiel E, Schneider T (2011). Evidence for the cure of HIVinfection by CCR5Δ32/Δ32 stem cell transplantation. Blood 117:2791-2799

  • Anderson J, Akkina R (2005). HIV-1 resistance conferred bysiRNA cosuppression of CXCR4 and CCR5 coreceptors by a bispecific lentiviral vector. AIDS research and therapy 2:1

  • Archin NM, Liberty A, Kashuba AD, Choudhary SK, Kuruc J,Crooks A, Parker D, Anderson E, Kearney M, Strain M (2012).Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature 487:482

  • Bogerd HP, Kornepati AV, Marshall JB, Kennedy EM, Cullen BR(2015). Specific induction of endogenous viral restriction factorsusing CRISPR/Cas-derived transcriptional activators.Proceedings of the National Academy of Sciences 112:E7249- E7256

  • Bowers NL, Helton ES, Huijbregts RP, Goepfert PA, Heath SL,Hel Z (2014). Immune suppression by neutrophils in HIV-1infection: role of PD-L1/PD-1 pathway. PLoS pathogens 10:e1003993

  • Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G,Rao S, Kazzaz Z, Bornstein E, Lambotte O, Altmann D (2006).Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nature medicine 12:1365

  • Brown TR (2015). I am the Berlin patient: a personal reflection. AIDS research and human retroviruses 31:2-3

  • Burnett JC, Zaia JA, Rossi JJ (2012). Creating genetic resistance to HIV. Current opinion in immunology 24:625-632

  • Cannon P, June C (2011). CCR5 knockout strategies. Current Opinion in HIV and AIDS 6:74

  • Cannon PM, Kohn DB, Kiem H-P (2014). HIV eradication— from Berlin to Boston. Nature biotechnology 32:315

  • Cardarelli F, Digiacomo L, Marchini C, Amici A, Salomone F,Fiume G, Rossetta A, Gratton E, Pozzi D, Caracciolo G (2016).The intracellular trafficking mechanism of Lipofectamine-basedtransfection reagents and its implication for gene delivery. Scientific reports 6:25879

  • Chemudupati M, Kenney AD, Bonifati S, Zani A, McMichaelTM, Wu L, Yount JS (2019). From APOBEC to ZAP: diversemechanisms used by cellular restriction factors to inhibit virusinfections. Biochimica Et Biophysica Acta (BBA)-Molecular Cell Research 1866:382-394

  • Cho SW, Kim S, Kim JM, Kim J-S (2013). Targeted genomeengineering in human cells with the Cas9 RNA-guided endonuclease. Nature biotechnology 31:230

  • Chun T-W, Nickle DC, Justement JS, Meyers JH, Roby G,Hallahan CW, Kottilil S, Moir S, Mican JM, Mullins JI (2008).Persistence of HIV in gut-associated lymphoid tissue despitelong-term antiretroviral therapy. The Journal of infectious diseases 197:714-720

  • Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC,Lusso P (1995). Identification of RANTES, MIP-1α, and MIP-1βas the major HIV-suppressive factors produced by CD8+ T cells. Science 270:1811-1815

  • Cohen MS, Shaw GM, McMichael AJ, Haynes BF (2011). AcuteHIV-1 infection. New England Journal of Medicine 364:1943-Corrigan-Curay J, O'reilly M, Kohn DB, Cannon PM, Bao G,Bushman FD, Carroll D, Cathomen T, Joung JK, Roth D (2015).Genome Editing Technologies: Defining a Path to Clinic:Genomic Editing: Establishing Preclinical Toxicology Standards,Bethesda, Maryland 10 June 2014. Molecular Therapy 23:796-806Cox DB, Gootenberg JS, Abudayyeh OO, Franklin B, Kellner MJ,Joung J, Zhang F (2017). RNA editing with CRISPR-Cas13. Science 358:1019-1027

  • Crudele JM, Chamberlain JS (2018). Cas9 immunity createschallenges for CRISPR gene editing therapies. Nature communications 9:3497

  • Cyranoski D, Ledford H (2018). Genome-edited baby claim provokes international outcry. Nature 563:607-608

  • De Ravin SS, Li L, Wu X, Choi U, Allen C, Koontz S, Lee J,Theobald-Whiting N, Chu J, Garofalo M (2017). CRISPR-Cas9gene repair of hematopoietic stem cells from patients with X-linked chronic granulomatous disease. Science Translational Medicine 9:eaah3480

  • Duan J, Lu G, Xie Z, Lou M, Luo J, Guo L, Zhang Y (2014).Genome-wide identification of CRISPR/Cas9 off-targets in human genome. Cell research 24:1009

  • Ebina H, Misawa N, Kanemura Y, Koyanagi Y (2013).Harnessing the CRISPR/Cas9 system to disrupt latent HIV-1 provirus. Scientific reports 3:2510

  • Finzi D, Blankson J, Siliciano JD, Margolick JB, Chadwick K,Pierson T, Smith K, Lisziewicz J, Lori F, Flexner C (1999). Latentinfection of CD4+ T cells provides a mechanism for lifelongpersistence of HIV-1, even in patients on effective combination therapy. Nature medicine 5:512

  • Finzi D, Hermankova M, Pierson T, Carruth LM, Buck C,Chaisson RE, Quinn TC, Chadwick K, Margolick J, BrookmeyerR (1997). Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278:1295-1300

  • Fischer-Smith T, Croul S, Sverstiuk AE, Capini C, L’Heureux D,Régulier EG, Richardson MW, Amini S, Morgello S, Khalili K(2001). CNS invasion by CD14+/CD16+ peripheral blood-derived monocytes in HIV dementia: perivascular accumulationand reservoir of HIV infection. Journal of neurovirology 7:528-Fletcher CV, Staskus K, Wietgrefe SW, Rothenberger M, Reilly C,Chipman JG, Beilman GJ, Khoruts A, Thorkelson A, Schmidt TE(2014). Persistent HIV-1 replication is associated with lowerantiretroviral drug concentrations in lymphatic tissues.Proceedings of the National Academy of Sciences 111:2307-2312Fornaguera C, Dols-Perez A, Caldero G, Garcia-Celma M,Camarasa J, Solans C (2015). PLGA nanoparticles prepared bynano-emulsion templating using low-energy methods as efficientnanocarriers for drug delivery across the blood–brain barrier. Journal of controlled release 211:134-143

  • Fu Y, Sander JD, Reyon D, Cascio VM, Joung JK (2014).

  • Gaj T, Gersbach CA, Barbas III CF (2013). ZFN, TALEN, andCRISPR/Cas-based methods for genome engineering. Trends in biotechnology 31:397-405

  • Gallastegui E, Millán-Zambrano G, Terme J-M, Chávez S, JordanA (2011). Chromatin reassembly factors are involved intranscriptional interference promoting HIV latency. Journal of virology 85:3187-3202

  • Gilbert LA, Larson MH, Morsut L, Liu Z, Brar GA, Torres SE,Stern-Ginossar N, Brandman O, Whitehead EH, Doudna JA(2013). CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 154:442-451

  • Givens BE, Naguib YW, Geary SM, Devor EJ, Salem AK (2018).Nanoparticle-based delivery of CRISPR/Cas9 genome-editing therapeutics. The AAPS journal 20:108

  • Glass WG, Lim JK, Cholera R, Pletnev AG, Gao J-L, Murphy PM(2005). Chemokine receptor CCR5 promotes leukocytetrafficking to the brain and survival in West Nile virus infection. Journal of Experimental Medicine 202:1087-1098

  • Gonzalez-Enriquez GV, Escoto-Delgadillo M, Vazquez-Valls E,Torres-Mendoza BM (2017). SERINC as a Restriction Factor toInhibit Viral Infectivity and the Interaction with HIV. Journal of immunology research 2017:

  • Henrich TJ, Hu Z, Li JZ, Sciaranghella G, Busch MP, KeatingSM, Gallien S, Lin NH, Giguel FF, Lavoie L (2013). Long-termreduction in peripheral blood HIV type 1 reservoirs followingreduced-intensity conditioning allogeneic stem celltransplantation. The Journal of infectious diseases 207:1694-1702Hladik F, McElrath MJ (2008). Setting the stage: host invasion by HIV. Nature Reviews Immunology 8:447

  • Hoffmann C (2007). The epidemiology of HIV coreceptor tropism. European journal of medical research 12:385

  • Holt N, Wang J, Kim K, Friedman G, Wang X, Taupin V, CrooksGM, Kohn DB, Gregory PD, Holmes MC (2010). Humanhematopoietic stem/progenitor cells modified by zinc-fingernucleases targeted to CCR5 control HIV-1 in vivo. Nature biotechnology 28:839

  • Hsu PD, Lander ES, Zhang F (2014). Development andapplications of CRISPR-Cas9 for genome engineering. Cell 157:1262-1278

  • Hu W, Kaminski R, Yang F, Zhang Y, Cosentino L, Li F, Luo B,Alvarez-Carbonell D, Garcia-Mesa Y, Karn J (2014). RNA-directed gene editing specifically eradicates latent and preventsnew HIV-1 infection. Proceedings of the National Academy of Sciences 111:11461-11466

  • Huang Y, Paxton WA, Wolinsky SM, Neumann AU, Zhang L,He T, Kang S, Ceradini D, Jin Z, Yazdanbakhsh K (1996). Therole of a mutant CCR5 allele in HIV–1 transmission and disease progression. Nature medicine 2:1240

  • Hütter G (2014). More on shift of HIV tropism in stem-celltransplantation with CCR5 delta32/delta32 mutation. The New England journal of medicine 371:2437-2438

  • Hütter G, Nowak D, Mossner M, Ganepola S, Müßig A, Allers K,Schneider T, Hofmann J, Kücherer C, Blau O (2009). Long-termcontrol of HIV by CCR5 Delta32/Delta32 stem-celltransplantation. New England Journal of Medicine 360:692-698Ishino Y, Shinagawa H, Makino K, Amemura M, Nakata A(1987). Nucleotide sequence of the iap gene, responsible foralkaline phosphatase isozyme conversion in Escherichia coli, andidentification of the gene product. Journal of bacteriologyJinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA,Charpentier E (2012). A programmable dual-RNA–guided DNAendonuclease in adaptive bacterial immunity. science 337:816-Karanam K, Kafri R, Loewer A, Lahav G (2012). Quantitative livecell imaging reveals a gradual shift between DNA repairmechanisms and a maximal use of HR in mid S phase. Molecular cell 47:320-329

  • Khalili K, White MK, Jacobson JM (2017). Novel AIDS therapiesbased on gene editing. Cellular and Molecular Life SciencesKim V, Mears BM, Powell BH, Witwer KW (2017). MutantCas9-transcriptional activator activates HIV-1 in U1 cells in thepresence and absence of LTR-specific guide RNAs. Matters 2017:Kim Y, Anderson JL, Lewin SR (2018). Getting the “kill” into“shock and kill”: strategies to eliminate latent HIV. Cell host & microbe 23:14-26

  • Kimberland ML, Hou W, Alfonso-Pecchio A, Wilson S, Rao Y,Zhang S, Lu Q (2018). Strategies for controlling CRISPR/Cas9off-target effects and biological variations in mammalian genome editing experiments. Journal of biotechnology 284:91-101

  • Konermann S, Brigham MD, Trevino AE, Joung J, AbudayyehOO, Barcena C, Hsu PD, Habib N, Gootenberg JS, Nishimasu H(2015). Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature 517:583

  • Kuersten A, Wexler A (2019). Ten ways in which He Jiankui violated ethics. Nature biotechnology 37:19

  • Lahaye X, Gentili M, Silvin A, Conrad C, Picard L, Jouve M,Zueva E, Maurin M, Nadalin F, Knott GJ (2018). NONO detectsthe nuclear HIV capsid to promote cGAS-mediated innate immune activation. Cell 175:488-501. e422

  • Lederman MM, Cannon PM, Currier JS, June CH, Kiem HP,Kuritzkes DR, Lewin SR, Margolis DM, McCune JM, Mellors JW(2016). A cure for HIV infection:“not in my lifetime” or “just around the corner”? Pathogens & immunity 1:154

  • Lederman MM, Pike E (2017). Ten Years HIV Free: An Interviewwith “The Berlin Patient,” Timothy Ray Brown. Pathogens & immunity 2:422

  • Lenasi T, Contreras X, Peterlin BM (2008). Transcriptionalinterference antagonizes proviral gene expression to promote HIV latency. Cell host & microbe 4:123-133

  • Li C, Guan X, Du T, Jin W, Wu B, Liu Y, Wang P, Hu B, GriffinGE, Shattock RJ (2015). Inhibition of HIV-1 infection of primaryCD4+ T-cells by gene editing of CCR5 using adenovirus-delivered CRISPR/Cas9. Journal of General Virology 96:2381-Li J-r, Walker S, Nie J-b, Zhang X-q (2019). Experiments that ledto the first gene-edited babies: the ethical failings and the urgentneed for better governance. Journal of Zhejiang University- SCIENCE B 20:32-38

  • Li L, He Z-Y, Wei X-W, Gao G-P, Wei Y-Q (2015). Challenges inCRISPR/CAS9 delivery: potential roles of nonviral vectors. Human gene therapy 26:452-462

  • Rossi JJ (2005). Long-term inhibition of HIV-1 infection inprimary hematopoietic cells by lentiviral vector delivery of atriple combination of anti-HIV shRNA, anti-CCR5 ribozyme,and a nucleolar-localizing TAR decoy. Molecular TherapyLiang C, Wainberg MA, Das AT, Berkhout B (2016).CRISPR/Cas9: a double-edged sword when used to combat HIV infection. Retrovirology 13:37

  • Liao H-K, Gu Y, Diaz A, Marlett J, Takahashi Y, Li M, Suzuki K,Xu R, Hishida T, Chang C-J (2015). Use of the CRISPR/Cas9system as an intracellular defense against HIV-1 infection in human cells. Nature communications 6:6413

  • Lim KRQ, Yoon C, Yokota T (2018). Applications ofCRISPR/Cas9 for the treatment of Duchenne muscular dystrophy. Journal of personalized medicine 8:38

  • Limsirichai P, Gaj T, Schaffer DV (2016). CRISPR-mediatedactivation of latent HIV-1 expression. Molecular TherapyLin S, Staahl BT, Alla RK, Doudna JA (2014). Enhancedhomology-directed human genome engineering by controlled timing of CRISPR/Cas9 delivery. elife 3:e04766

  • Liu Q, Lai Y-T, Zhang P, Louder MK, Pegu A, Rawi R, AsokanM, Chen X, Shen C-H, Chuang G-Y (2019). Improvement ofantibody functionality by structure-guided paratope engraftment. Nature communications 10:721

  • Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R,MacDonald ME, Stuhlmann H, Koup RA, Landau NR (1996).Homozygous defect in HIV-1 coreceptor accounts for resistanceof some multiply-exposed individuals to HIV-1 infection. CellLiuzzi G, Chirianni A, Clementi M, Bagnarelli P, Valenza A,Cataldo PT, Piazza M (1996). Analysis of HIV-1 load in blood,semen and saliva: evidence for different viral compartments in across-sectional and longitudinal study. AIDS (London, England) 10:F51-56

  • Lopalco L (2010). CCR5: from natural resistance to a new anti- HIV strategy. Viruses 2:574-600

  • Louis Jeune V, Joergensen JA, Hajjar RJ, Weber T (2013). Pre-existing anti–adeno-associated virus antibodies as a challenge in AAV gene therapy. Human gene therapy methods 24:59-67

  • Maier DA, Brennan AL, Jiang S, Binder-Scholl GK, Lee G, PlesaG, Zheng Z, Cotte J, Carpenito C, Wood T (2013). Efficientclinical scale gene modification via zinc finger nuclease–targeteddisruption of the HIV co-receptor CCR5. Human gene therapyMcMahon D, Jones J, Wiegand A, Gange SJ, Kearney M, PalmerS, McNulty S, Metcalf J, Acosta E, Rehm C (2010). Short-courseraltegravir intensification does not reduce persistent low-levelviremia in patients with HIV-1 suppression during receipt ofcombination antiretroviral therapy. Clinical infectious diseasesMingozzi F, High KA (2013). Immune responses to AAV vectors:overcoming barriers to successful gene therapy. Blood, The Journal of the American Society of Hematology 122:23-36

  • Mingozzi F, Meulenberg JJ, Hui DJ, Basner-Tschakarjan E,Hasbrouck NC, Edmonson SA, Hutnick NA, Betts MR, KasteleinJJ, Stroes ES (2009). AAV-1–mediated gene transfer to skeletalmuscle in humans results in dose-dependent activation of capsid-specific T cells. Blood 114:2077-2086

  • Mitsuyasu RT, Merigan TC, Carr A, Zack JA, Winters MA,Workman C, Bloch M, Lalezari J, Becker S, Thornton L (2009).Phase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34+ cells. Nature medicine 15:285

  • Mojica FJ, Díez-Villaseñor C, García-Martínez J, Almendros C(2009). Short motif sequences determine the targets of theprokaryotic CRISPR defence system. Microbiology 155:733-740

  • Morgan RA, Walker R, Carter CS, Natarajan V, Tavel JA, BechtelC, Herpin B, Muul L, Zheng Z, Jagannatha S (2005). Preferentialsurvival of CD4+ T lymphocytes engineered with anti-humanimmunodeficiency virus (HIV) genes in HIV-infected individuals. Human gene therapy 16:1065-1074

  • Mout R, Ray M, Yesilbag Tonga G, Lee Y-W, Tay T, Sasaki K,Rotello VM (2017). Direct cytosolic delivery of CRISPR/Cas9-ribonucleoprotein for efficient gene editing. ACS nano 11:2452-Murray JM, Emery S, Kelleher AD, Law M, Chen J, Hazuda DJ,Nguyen B-YT, Teppler H, Cooper DA (2007). Antiretroviraltherapy with the integrase inhibitor raltegravir alters decaykinetics of HIV, significantly reducing the second phase. AidsMylvaganam GH, Silvestri G, Amara RR (2015). HIV therapeuticvaccines: moving towards a functional cure. Current opinion in immunology 35:1-8

  • Nair M, Guduru R, Liang P, Hong J, Sagar V, Khizroev S (2013).Externally controlled on-demand release of anti-HIV drug usingmagneto-electric nanoparticles as carriers. Nature communications 4:1707

  • Niethammer M, Tang CC, Vo A, Nguyen N, Spetsieris P,Dhawan V, Ma Y, Small M, Feigin A, During MJ (2018). Genetherapy reduces Parkinson’s disease symptoms by reorganizingfunctional brain connectivity. Science translational medicine 10:eaau0713

  • Palmer S, Maldarelli F, Wiegand A, Bernstein B, Hanna GJ, BrunSC, Kempf DJ, Mellors JW, Coffin JM, King MS (2008). Low-level viremia persists for at least 7 years in patients onsuppressive antiretroviral therapy. Proceedings of the National Academy of Sciences 105:3879-3884

  • Patel P, Ansari MY, Bapat S, Thakar M, Gangakhedkar R, JameelS (2014). The microRNA miR-29a is associated with human immunodeficiency virus latency. Retrovirology 11:108

  • Peluso MJ, Deeks SG, McCune JM (2019). HIV “cure”: A shot in the arm? EBioMedicine 42:3-5

  • Perez EE, Wang J, Miller JC, Jouvenot Y, Kim KA, Liu O, WangN, Lee G, Bartsevich VV, Lee Y-L (2008). Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nature biotechnology 26:808

  • Qin X-F, An DS, Chen IS, Baltimore D (2003). Inhibiting HIV-1infection in human T cells by lentiviral-mediated delivery ofsmall interfering RNA against CCR5. Proceedings of the National Academy of Sciences 100:183-188

  • Rasmussen TA, Tolstrup M, Brinkmann CR, Olesen R, ErikstrupC, Solomon A, Winckelmann A, Palmer S, Dinarello C, Buzon M(2014). Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressiveantiretroviral therapy: a phase 1/2, single group, clinical trial. The lancet HIV 1:e13-e21

  • McCauley SM, Nowosielska A, Antonarakis SE, Luban J (2015).HIV-1 Nef promotes infection by excluding SERINC5 from virion incorporation. Nature 526:212

  • Ruelas DS, Chan JK, Oh E, Heidersbach AJ, Hebbeler AM,Chavez L, Verdin E, Rape M, Greene WC (2015). MicroRNA-155 reinforces HIV latency. Journal of Biological ChemistrySaayman SM, Lazar DC, Scott TA, Hart JR, Takahashi M,Burnett JC, Planelles V, Morris KV, Weinberg MS (2016). Potentand targeted activation of latent HIV-1 using the CRISPR/dCas9 activator complex. Molecular therapy 24:488-498

  • Saez-Cirion A, Müller-Trutwin M (2019). The Yellow Brick Roadtowards HIV Eradication. Trends in immunology 40:465-467

  • Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber C-M, Saragosti S, Lapouméroulie C, Cognaux J, Forceille C (1996).Resistance to HIV-1 infection in caucasian individuals bearingmutant alleles of the CCR-5 chemokine receptor gene. Nature 382:722

  • Sather BD, Ibarra GSR, Sommer K, Curinga G, Hale M, Khan IF,Singh S, Song Y, Gwiazda K, Sahni J (2015). Efficientmodification of CCR5 in primary human hematopoietic cellsusing a megaTAL nuclease and AAV donor template. Science translational medicine 7:307ra156-307ra156

  • Sharp PM, Hahn BH (2010). The evolution of HIV-1 and theorigin of AIDS. Philos Trans R Soc Lond B Biol Sci 365:2487-Sharp PM, Hahn BH (2011). Origins of HIV and the AIDSpandemic. Cold Spring Harbor perspectives in medicine 1:a006841

  • Shen B, Zhang W, Zhang J, Zhou J, Wang J, Chen L, Wang L,Hodgkins A, Iyer V, Huang X (2014). Efficient genomemodification by CRISPR-Cas9 nickase with minimal off-target effects. Nature methods 11:399

  • Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K,Margolick JB, Kovacs C, Gange SJ, Siliciano RF (2003). Long-term follow-up studies confirm the stability of the latentreservoir for HIV-1 in resting CD4+ T cells. Nature medicineSM Wold W, Toth K (2013). Adenovirus vectors for genetherapy, vaccination and cancer gene therapy. Current gene therapy 13:421-433

  • Smith PD, Meng G, Salazar‐Gonzalez JF, Shaw GM (2003).Macrophage HIV‐1 infection and the gastrointestinal tract reservoir. Journal of leukocyte biology 74:642-649

  • Sunshine S, Kirchner R, Amr SS, Mansur L, Shakhbatyan R, KimM, Bosque A, Siliciano RF, Planelles V, Hofmann O (2016). HIVintegration site analysis of cellular models of HIV latency with aprobe-enriched next-generation sequencing assay. Journal of virology 90:4511-4519

  • Trobridge GD (2011). Genotoxicity of retroviral hematopoieticstem cell gene therapy. Expert opinion on biological therapyVakulskas CA, Dever DP, Rettig GR, Turk R, Jacobi AM,Collingwood MA, Bode NM, McNeill MS, Yan S, Camarena J(2018). A high-fidelity Cas9 mutant delivered as aribonucleoprotein complex enables efficient gene editing inhuman hematopoietic stem and progenitor cells. Nature medicine 24:1216

  • van Lunzen J (2007). How will CCR5 antagonists influence therecommendations for the antiretroviral treatment of HIV-1 infection. European journal of medical research 12:435

  • van Lunzen J, Fehse B, Hauber J (2011). Gene therapy strategies: can we eradicate HIV? Current HIV/AIDS Reports 8:78-84

  • Van Lunzen J, Glaunsinger T, Stahmer I, Von Baehr V, Baum C,Schilz A, Kuehlcke K, Naundorf S, Martinius H, Hermann F(2007). Transfer of autologous gene-modified T cells in HIV-infected patients with advanced immunodeficiency and drug- resistant virus. Molecular Therapy 15:1024-1033

  • Walker R, Michael Blacsc R, Carter CS, Chang L, Klein H,Clifford Lane H, Leilman SF, Mullen CA (1993). A study of thesafety and survival of the adoptive transfer of genetically markedsyngeneic lymphocytes in HIV-infected identical twins. Human gene therapy 4:659-680

  • Walker-Sperling VE, Pohlmeyer CW, Tarwater PM, Blankson JN(2016). The effect of latency reversal agents on primary CD8+ Tcells: implications for shock and kill strategies for humanimmunodeficiency virus eradication. EBioMedicine 8:217-229

  • Wang CX, Cannon PM (2016). The clinical applications ofgenome editing in HIV. Blood, The Journal of the American Society of Hematology 127:2546-2552

  • Wang G, Zhao N, Berkhout B, Das AT (2016). CRISPR-Cas9 caninhibit HIV-1 replication but NHEJ repair facilitates virus escape. Molecular Therapy 24:522-526

  • Wang Q, Liu S, Liu Z, Ke Z, Li C, Yu X, Chen S, Guo D (2018).Genome scale screening identification of SaCas9/gRNAs fortargeting HIV-1 provirus and suppression of HIV-1 infection. Virus research 250:21-30

  • Wang W, Ye C, Liu J, Zhang D, Kimata JT, Zhou P (2014). CCR5gene disruption via lentiviral vectors expressing Cas9 and singleguided RNA renders cells resistant to HIV-1 infection. PloS one 9:e115987

  • Wei X, Nielsen R (2019). CCR5-∆ 32 is deleterious in the homozygous state in humans. Nature medicine 1

  • Wyvekens N, Topkar VV, Khayter C, Joung JK, Tsai SQ (2015).Dimeric CRISPR RNA-guided FokI-dCas9 nucleases directed bytruncated gRNAs for highly specific genome editing. Human gene therapy 26:425-431

  • Xiao Q, Guo D, Chen S (2019). Application of CRISPR/Cas9-based gene editing in HIV-1/AIDS therapy. Frontiers in Cellular and Infection Microbiology 9:69

  • Xu L, Yang H, Gao Y, Chen Z, Xie L, Liu Y, Liu Y, Wang X, Li H,Lai W (2017). CRISPR/Cas9-mediated CCR5 ablation in humanhematopoietic stem/progenitor cells confers HIV-1 resistance in vivo. Molecular Therapy 25:1782-1789

  • Yang A-G, Bai X, Huang XF, Yao C, Chen S-Y (1997).Phenotypic knockout of HIV type 1 chemokine coreceptor CCR-5 by intrakines as potential therapeutic approach for HIV-1infection. Proceedings of the National Academy of SciencesYe L, Wang J, Beyer AI, Teque F, Cradick TJ, Qi Z, Chang JC,Bao G, Muench MO, Yu J (2014). Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5Δ32mutation confers resistance to HIV infection. Proceedings of the National Academy of Sciences 111:9591-9596

  • Yin H, Song C-Q, Dorkin JR, Zhu LJ, Li Y, Wu Q, Park A, YangJ, Suresh S, Bizhanova A (2016). Therapeutic genome editing by

  • Yoder KE, Bundschuh R (2016). Host double strand break repairgenerates HIV-1 strains resistant to CRISPR/Cas9. Scientific reports 6:29530

  • Yoder KE, Panfil AR, London JA, Green PL (2018).CRISPR/Cas9 genome editing to disable the latent HIV-1 provirus. Frontiers in microbiology 9:3107

  • Yucel D, Kocabas F (2017) Developments in Hematopoietic StemCell Expansion and Gene Editing Technologies. In: Cell Biologyand Translational Medicine, Volume 1. Springer, pp 103-125

  • Yukl SA, Shergill A, McQuaid K, Gianella S, Lampiris H, HareCB, Pandori M, Sinclair E, Günthard HF, Fischer M (2010).Effect of raltegravir-containing intensification on HIV burdenand T cell activation in multiple Gut sites of HIV+ adults onsuppressive antiretroviral therapy. AIDS (London, England)Yurkovetskiy L, Guney MH, Kim K, Goh SL, McCauley S,Dauphin A, Diehl WE, Luban J (2018). Primateimmunodeficiency virus proteins Vpx and Vpr counteracttranscriptional repression of proviruses by the HUSH complex. Nature microbiology 3:1354

  • Zaiss A, Muruve D (2008). Immunity to adeno-associated virusvectors in animals and humans: a continued challenge. Gene therapy 15:808

  • Zetsche B, Gootenberg JS, Abudayyeh OO, Slaymaker IM,Makarova KS, Essletzbichler P, Volz SE, Joung J, Van Der Oost J,Regev A (2015). Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell 163:759-771

  • Zhang Y, Yin C, Zhang T, Li F, Yang W, Kaminski R, Fagan PR,Putatunda R, Young W-B, Khalili K (2015). CRISPR/gRNA-directed synergistic activation mediator (SAM) induces specific,persistent and robust reactivation of the HIV-1 latent reservoirs. Scientific reports 5:16277

  • Zhou M, Greenhill S, Huang S, Silva TK, Sano Y, Wu S, Cai Y,Nagaoka Y, Sehgal M, Cai DJ (2016). CCR5 is a suppressor forcortical plasticity and hippocampal learning and memory. ElifeZhou W, Ma D, Sun AX, Tran H-D, Ma D-l, Singh BK, Zhou J,Zhang J, Wang D, Zhao Y (2018). PD-linked CHCHD2mutations impair CHCHD10 and MICOS complex leading tomitochondria dysfunction. Human molecular genetics 28:1100-

                                                                                                                                                                                                        
  • Article Statistics