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2000
Volume 25, Issue 4
  • ISSN: 1566-5232
  • E-ISSN: 1875-5631

Abstract

The immune system presents significant obstacles to gene therapy, which has limited its use in treating many illnesses. New approaches are needed to overcome these problems and improve the effectiveness of gene therapy. This study explores several techniques to immune regulation within gene therapy, a cutting-edge discipline that aims to optimise results by fine-tuning the immune response. We cover new ways to control the immune system and deliver therapeutic genes just where they are needed, including influencing immunological checkpoints, causing immunotolerance, and making smart use of immunomodulatory drugs. In addition, the study provides insight into new developments in the design of less immunogenic gene delivery vectors, which allow for the extension of transgene expression with minimal adverse immune reactions. In order to maximise the efficacy of gene-based therapies, this review analyses these novel approaches and gives a thorough overview of the present state of the art by addressing obstacles and pointing the way toward future developments in immune regulation. Not only does their integration provide new opportunities for the creation of safer and more effective gene treatments, but it also contains the key to overcome current obstacles.

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2025-10-16

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References

  1. ShirleyJ.L. de JongY.P. TerhorstC. HerzogR.W. Immune responses to viral gene therapy vectors.Mol. Ther.202028370972210.1016/j.ymthe.2020.01.00131968213
     [Google Scholar]
  2. FreitasM.V. FrâncioL. HalevaL. MatteU.S. Protection is not always a good thing: The immune system’s impact on gene therapy.Genet. Mol. Biol.2022453) (suppl 1e2022004610.1590/1678‑4685‑gmb‑2022‑004635852088
     [Google Scholar]
  3. PollardA.J. BijkerE.M. A guide to vaccinology: from basic principles to new developments.Nat. Rev. Immunol.20212128310010.1038/s41577‑020‑00479‑733353987
     [Google Scholar]
  4. VinayD.S. RyanE.P. PawelecG. TalibW.H. StaggJ. ElkordE. LichtorT. DeckerW.K. WhelanR.L. KumaraH.M.C.S. SignoriE. HonokiK. GeorgakilasA.G. AminA. HelferichW.G. BoosaniC.S. GuhaG. CirioloM.R. ChenS. MohammedS.I. AzmiA.S. KeithW.N. BilslandA. BhaktaD. HalickaD. FujiiH. AquilanoK. AshrafS.S. NowsheenS. YangX. ChoiB.K. KwonB.S. Immune evasion in cancer: Mechanistic basis and therapeutic strategies.Semin. Cancer Biol.201535Suppl.S185S19810.1016/j.semcancer.2015.03.00425818339
     [Google Scholar]
  5. NairS. Personalized medicine: Striding from genes to medicines.Perspect. Clin. Res.20101414615010.4103/2229‑3485.7177521350731
     [Google Scholar]
  6. Razi SoofiyaniS. BaradaranB. LotfipourF. KazemiT. MohammadnejadL. Gene therapy, early promises, subsequent problems, and recent breakthroughs.Adv. Pharm. Bull.20133224925524312844
     [Google Scholar]
  7. DasS.K. MenezesM.E. BhatiaS. WangX.Y. EmdadL. SarkarD. FisherP.B. Gene therapies for cancer: Strategies, challenges and successes.J. Cell. Physiol.2015230225927110.1002/jcp.2479125196387
     [Google Scholar]
  8. BulchaJ.T. WangY. MaH. TaiP.W.L. GaoG. Viral vector platforms within the gene therapy landscape.Signal Transduct. Target. Ther.2021615310.1038/s41392‑021‑00487‑633558455
     [Google Scholar]
  9. NayakS. HerzogR.W. Progress and prospects: immune responses to viral vectors.Gene Ther.201017329530410.1038/gt.2009.14819907498
     [Google Scholar]
  10. TraviesoT. LiJ. MaheshS. MelloJ.D.F.R.E. BlasiM. The use of viral vectors in vaccine development.Vaccines20227111036679846
     [Google Scholar]
  11. MendonçaS.A. LorinczR. BoucherP. CurielD.T. Adenoviral vector vaccine platforms in the SARS-CoV-2 pandemic.Vaccines20216111435062662
     [Google Scholar]
  12. MarshallJ.S. WarringtonR. WatsonW. KimH.L. An introduction to immunology and immunopathology.Allergy Asthma Clin. Immunol.201814S2Suppl. 24910.1186/s13223‑018‑0278‑130263032
     [Google Scholar]
  13. Amarante-MendesG.P. AdjemianS. BrancoL.M. ZanettiL.C. WeinlichR. BortoluciK.R. Pattern recognition receptors and the host cell death molecular machinery.Front. Immunol.20189237910.3389/fimmu.2018.0237930459758
     [Google Scholar]
  14. BulutO. KilicG. Domínguez-AndrésJ. Immune memory in aging: A wide perspective covering microbiota, brain, metabolism, and epigenetics.Clin. Rev. Allergy Immunol.202163349952910.1007/s12016‑021‑08905‑x34910283
     [Google Scholar]
  15. BurrellC.J. HowardC.R. MurphyF.A. Epidemiology of viral infections.Fenner White’s Med Virol2017185
     [Google Scholar]
  16. KranichJ. KrautlerN.J. How follicular dendritic cells shape the b-cell antigenome.Front. Immunol.2016722510.3389/fimmu.2016.0022527446069
     [Google Scholar]
  17. PalmA.K.E. HenryC. Remembrance of things past: Long-term B cell memory after infection and vaccination.Front. Immunol.201910178710.3389/fimmu.2019.0178731417562
     [Google Scholar]
  18. JamesL.K. B cells defined by immunoglobulin isotypes.Clin. Exp. Immunol.2022210323023910.1093/cei/uxac09136197112
     [Google Scholar]
  19. CysterJ.G. AllenC.D.C. B cell responses - Cell interaction dynamics and decisions.Cell2019177352454010.1016/j.cell.2019.03.01631002794
     [Google Scholar]
  20. RaskovH. OrhanA. ChristensenJ.P. GögenurI. Cytotoxic CD8+ T cells in cancer and cancer immunotherapy.Br. J. Cancer2021124235936710.1038/s41416‑020‑01048‑432929195
     [Google Scholar]
  21. GoverdhanaS. PuntelM. XiongW. ZirgerJ.M. BarciaC. CurtinJ.F. SofferE.B. MondkarS. KingG.D. HuJ. SciasciaS.A. CandolfiM. GreengoldD.S. LowensteinP.R. CastroM.G. Regulatable gene expression systems for gene therapy applications: progress and future challenges.Mol. Ther.200512218921110.1016/j.ymthe.2005.03.02215946903
     [Google Scholar]
  22. KumarA. DasS.K. EmdadL. FisherP.B. Applications of tissue-specific and cancer-selective gene promoters for cancer diagnosis and therapy.Adv. Cancer Res.202316025331510.1016/bs.acr.2023.03.00537704290
     [Google Scholar]
  23. HackettP.B. LargaespadaD.A. SwitzerK.C. CooperL.J.N. Evaluating risks of insertional mutagenesis by DNA transposons in gene therapy.Transl. Res.2013161426528310.1016/j.trsl.2012.12.00523313630
     [Google Scholar]
  24. RomanoG. Development of safer gene delivery systems to minimize the risk of insertional mutagenesis-related malignancies: a critical issue for the field of gene therapy.ISRN Oncol.2012201211410.5402/2012/61631023209944
     [Google Scholar]
  25. RonzittiG. GrossD.A. MingozziF. Human immune responses to adeno-associated virus (AAV) vectors.Front. Immunol.20201167010.3389/fimmu.2020.0067032362898
     [Google Scholar]
  26. ZhanW. MuhuriM. TaiP.W.L. GaoG. Vectored immunotherapeutics for infectious diseases: Can rAAVs be the game changers for fighting transmissible pathogens?Front. Immunol.20211267369910.3389/fimmu.2021.67369934046041
     [Google Scholar]
  27. SackB.K. HerzogR.W. Evading the immune response upon in vivo gene therapy with viral vectors.Curr. Opin. Mol. Ther.200911549350319806497
     [Google Scholar]
  28. BüningH. SrivastavaA. Capsid modifications for targeting and improving the efficacy of AAV vectors.Mol. Ther. Methods Clin. Dev.20191224826510.1016/j.omtm.2019.01.00830815511
     [Google Scholar]
  29. HamiltonB.A. WrightJ.F. Challenges posed by immune responses to AAV vectors: Addressing root causes.Front. Immunol.20211267589710.3389/fimmu.2021.67589734084173
     [Google Scholar]
  30. GurdaB.L. RauppC. Popa-WagnerR. NaumerM. OlsonN.H. NgR. McKennaR. BakerT.S. KleinschmidtJ.A. Agbandje-McKennaM. Mapping a neutralizing epitope onto the capsid of adeno-associated virus serotype 8.J. Virol.201286157739775110.1128/JVI.00218‑1222593150
     [Google Scholar]
  31. RaguramA. BanskotaS. LiuD.R. Therapeutic in vivo delivery of gene editing agents.Cell2022185152806282710.1016/j.cell.2022.03.04535798006
     [Google Scholar]
  32. PrasadS. DimmockD.P. GreenbergB. WaliaJ.S. SadhuC. TavakkoliF. LipshutzG.S. Immune responses and immunosuppressive strategies for adeno-associated virus-based gene therapy for treatment of central nervous system disorders: Current knowledge and approaches.Hum. Gene Ther.20223323-241228124510.1089/hum.2022.13835994385
     [Google Scholar]
  33. SassoE. D’AliseA.M. ZambranoN. ScarselliE. FolgoriA. NicosiaA. New viral vectors for infectious diseases and cancer.Semin. Immunol.20205010143010.1016/j.smim.2020.10143033262065
     [Google Scholar]
  34. ElangkovanN. DicksonG. Gene therapy for duchenne muscular dystrophy.J. Neuromuscul. Dis.20218Suppl. 2S303S31610.3233/JND‑21067834511510
     [Google Scholar]
  35. ArrudaV.R. Samelson-JonesB.J. Gene therapy for immune tolerance induction in hemophilia with inhibitors.J. Thromb. Haemost.20161461121113410.1111/jth.1333127061380
     [Google Scholar]
  36. SlepickaP.F. YazdanifarM. BertainaA. Harnessing mechanisms of immune tolerance to improve outcomes in solid organ transplantation: A review.Front. Immunol.20211268846010.3389/fimmu.2021.68846034177941
     [Google Scholar]
  37. XingY. HogquistK.A. T-cell tolerance: central and peripheral.Cold Spring Harb. Perspect. Biol.201246a00695710.1101/cshperspect.a00695722661634
     [Google Scholar]
  38. SakaguchiS. YamaguchiT. NomuraT. OnoM. Regulatory T cells and immune tolerance.Cell2008133577578710.1016/j.cell.2008.05.00918510923
     [Google Scholar]
  39. RuizR. KirkA.D. Long-term toxicity of immunosuppressive therapy.Transplantation of the LiverElsevier2015135410.1016/B978‑1‑4557‑0268‑8.00097‑X
     [Google Scholar]
  40. TaamsL.S. PalmerD.B. AkbarA.N. RobinsonD.S. BrownZ. HawrylowiczC.M. Regulatory T cells in human disease and their potential for therapeutic manipulation.Immunology200611811910.1111/j.1365‑2567.2006.02348.x16630018
     [Google Scholar]
  41. EwaishaR. AndersonK.S. Immunogenicity of CRISPR therapeutics—Critical considerations for clinical translation.Front. Bioeng. Biotechnol.202311113859610.3389/fbioe.2023.113859636873375
     [Google Scholar]
  42. WenH. JungH. LiX. Drug delivery approaches in addressing clinical pharmacology-related issues: Opportunities and challenges.AAPS J.20151761327134010.1208/s12248‑015‑9814‑926276218
     [Google Scholar]
  43. KhanS. UllahM.W. SiddiqueR. NabiG. MananS. YousafM. Role of recombinant DNA technology to improve lifeInt. J. Genom.20162016240595410.1155/2016/2405954
     [Google Scholar]
  44. UddinF. RudinC.M. SenT. CRISPR gene therapy: Applications, limitations, and implications for the future.Front. Oncol.202010138710.3389/fonc.2020.0138732850447
     [Google Scholar]
  45. RamamoorthM. NarvekarA. Non viral vectors in gene therapy- an overview.J. Clin. Diagn. Res.201591GE01GE0610.7860/JCDR/2015/10443.539425738007
     [Google Scholar]
  46. NayerossadatN. MaedehT. AliP. Viral and nonviral delivery systems for gene delivery.Adv. Biomed. Res.2012112710.4103/2277‑9175.9815223210086
     [Google Scholar]
  47. ShchaslyvyiA.Y. AntonenkoS.V. TesliukM.G. TelegeevG.D. Current state of human gene therapy: Approved products and vectors.Pharmaceuticals (Basel)20231610141610.3390/ph1610141637895887
     [Google Scholar]
  48. ZhengD. LiwinskiT. ElinavE. Interaction between microbiota and immunity in health and disease.Cell Res.202030649250610.1038/s41422‑020‑0332‑732433595
     [Google Scholar]
  49. KaechS.M. WherryE.J. AhmedR. Effector and memory T-cell differentiation: implications for vaccine development.Nat. Rev. Immunol.20022425126210.1038/nri77812001996
     [Google Scholar]
  50. ShayakhmetovD.M. Di PaoloN.C. MossmanK.L. Recognition of virus infection and innate host responses to viral gene therapy vectors.Mol. Ther.20101881422142910.1038/mt.2010.12420551916
     [Google Scholar]
  51. AhrendsT. BorstJ. The opposing roles of CD 4+ T cells in anti-tumour immunity.Immunology2018154458259210.1111/imm.1294129700809
     [Google Scholar]
  52. ChinnasamyD. MilsomM.D. ShafferJ. NeuenfeldtJ. ShaabanA.F. MargisonG.P. FairbairnL.J. ChinnasamyN. Multicistronic lentiviral vectors containing the FMDV 2A cleavage factor demonstrate robust expression of encoded genes at limiting MOI.Virol. J.2006311410.1186/1743‑422X‑3‑1416539700
     [Google Scholar]
  53. RoyS. ClawsonD.S. LavrukhinO. SandhuA. MillerJ. WilsonJ.M. Rescue of chimeric adenoviral vectors to expand the serotype repertoire.J. Virol. Methods20071411142110.1016/j.jviromet.2006.11.02217197043
     [Google Scholar]
  54. AhmedS.S. LiJ. GodwinJ. GaoG. ZhongL. Gene transfer in the liver using recombinant adeno-associated virus.Curr. Protoc. Microbiol.2013141610.1002/9780471729259.mc14d06s29
     [Google Scholar]
  55. FogagnoloA. CampoG.C. MariM. PompeiG. PavasiniR. VoltaC.A. SpadaroS. The underestimated role of platelets in severe infection a narrative review.Cells202211342410.3390/cells1103042435159235
     [Google Scholar]
  56. GritsenkoA. YuS. Martin-SanchezF. Diaz-del-OlmoI. NicholsE.M. DavisD.M. BroughD. Lopez-CastejonG. Priming is dispensable for NLRP3 inflammasome activation in human monocytes in vitro. Front. Immunol.20201156592410.3389/fimmu.2020.56592433101286
     [Google Scholar]
  57. KuzmichN. SivakK. ChubarevV. PorozovY. Savateeva-LyubimovaT. PeriF. TLR4 signaling pathway modulators as potential therapeutics in inflammation and sepsis.Vaccines (Basel)2017543410.3390/vaccines504003428976923
     [Google Scholar]
  58. ErtlH.C.J. Immunogenicity and toxicity of AAV gene therapy.Front. Immunol.20221397580310.3389/fimmu.2022.97580336032092
     [Google Scholar]
  59. BarnesP.J. How corticosteroids control inflammation: Quintiles Prize Lecture 2005.Br. J. Pharmacol.2006148324525410.1038/sj.bjp.070673616604091
     [Google Scholar]
  60. MukherjeeS. MukherjeeU. A comprehensive review of immunosuppression used for liver transplantation.J. Transplant.2009200912010.1155/2009/70146420130772
     [Google Scholar]
  61. NiemannB. PuleoA. StoutC. MarkelJ. BooneB.A. Biologic functions of hydroxychloroquine in disease: From COVID-19 to cancer.Pharmaceutics20221412255110.3390/pharmaceutics1412255136559044
     [Google Scholar]
  62. CoutinhoA.E. ChapmanK.E. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights.Mol. Cell. Endocrinol.2011335121310.1016/j.mce.2010.04.00520398732
     [Google Scholar]
  63. MitraR. Adverse effects of corticosteroids on bone metabolism: a review.PM R20113546647110.1016/j.pmrj.2011.02.01721570035
     [Google Scholar]
  64. PollizziK.N. PowellJ.D. Regulation of T cells by mTOR: the known knowns and the known unknowns.Trends Immunol.2015361132010.1016/j.it.2014.11.00525522665
     [Google Scholar]
  65. AgrawalS. ZaritskyJ.J. FornoniA. SmoyerW.E. Dyslipidaemia in nephrotic syndrome: mechanisms and treatment.Nat. Rev. Nephrol.2018141577010.1038/nrneph.2017.15529176657
     [Google Scholar]
  66. PaniriA. HosseiniM.M. RasoulinejadA. Akhavan-NiakiH. Molecular effects and retinopathy induced by hydroxychloroquine during SARS-CoV-2 therapy: Role of CYP450 isoforms and epigenetic modulations.Eur. J. Pharmacol.202088617345410.1016/j.ejphar.2020.17345432763298
     [Google Scholar]
  67. EspandarG. MoghimiJ. GhorbaniR. PouraziziM. SeiriM.A. KhosraviS. Retinal toxicity in patients treated with hydroxychloroquine: A cross-sectional study.Med. Hypothesis Discov. Innov. Ophthalmol.201652414628293646
     [Google Scholar]
  68. MeleroI. Hervas-StubbsS. GlennieM. PardollD.M. ChenL. Immunostimulatory monoclonal antibodies for cancer therapy.Nat. Rev. Cancer2007729510610.1038/nrc2051
     [Google Scholar]
  69. DonnellyR.P. YoungH.A. RosenbergA.S. An overview of cytokines and cytokine antagonists as therapeutic agents.Ann. N. Y. Acad. Sci.20091182111310.1111/j.1749‑6632.2009.05382.x20074270
     [Google Scholar]
  70. VannemanM. DranoffG. Combining immunotherapy and targeted therapies in cancer treatment.Nat. Rev. Cancer201212423725110.1038/nrc323722437869
     [Google Scholar]
  71. SasoS. LoganK. AbdallahY. LouisL.S. Ghaem-MaghamiS. SmithJ.R. Del PrioreG. Use of cyclosporine in uterine transplantation.J. Transplant.2012201211110.1155/2012/13493622132302
     [Google Scholar]
  72. LeeH. MyoungH. KimS.M. Review of two immunosuppressants: tacrolimus and cyclosporine.J. Korean Assoc. Oral Maxillofac. Surg.202349631132310.5125/jkaoms.2023.49.6.31138155084
     [Google Scholar]
  73. BurkeJ.A. ZhangX. BobbalaS. FreyM.A. Bohorquez FuentesC. Freire HaddadH. AllenS.D. RichardsonR.A.K. AmeerG.A. ScottE.A. Subcutaneous nanotherapy repurposes the immunosuppressive mechanism of rapamycin to enhance allogeneic islet graft viability.Nat. Nanotechnol.202217331933010.1038/s41565‑021‑01048‑235039683
     [Google Scholar]
  74. BehrendM. Mycophenolate mofetil (Cellcept).Expert Opin. Investig. Drugs1998791509151910.1517/13543784.7.9.150915992049
     [Google Scholar]
  75. MolyneuxG. GibsonF.M. ChenC.M. MarwayH.K. McKeagS. MifsudC.V.J. PillingA.M. WhaymanM.J. TurtonJ.A. The haemotoxicity of azathioprine in repeat dose studies in the female CD-1 mouse.Int. J. Exp. Pathol.200889213815810.1111/j.1365‑2613.2008.00575.x18336531
     [Google Scholar]
  76. FerraraG. PetrilloM.G. GianiT. MarraniE. FilippeschiC. OrangesT. SimoniniG. CimazR. Clinical use and molecular action of corticosteroids in the pediatric age.Int. J. Mol. Sci.201920244410.3390/ijms2002044430669566
     [Google Scholar]
  77. LombardiY. FrançoisH. Belatacept in kidney transplantation: What are the true benefits? A systematic review.Front. Med. (Lausanne)2022994266510.3389/fmed.2022.94266535911396
     [Google Scholar]
  78. YaoX. WengG. WeiJ. GaoW. Basiliximab induction in kidney transplantation with donation after cardiac death donors.Exp. Ther. Med.20161162541254610.3892/etm.2016.323827284346
     [Google Scholar]
  79. Van AsscheG. SandbornW.J. FeaganB.G. SalzbergB.A. SilversD. MonroeP.S. PandakW.M. AndersonF.H. ValentineJ.F. WildG.E. GeenenD.J. SpragueR. TarganS.R. RutgeertsP. VexlerV. YoungD. ShamesR.S. Daclizumab, a humanised monoclonal antibody to the interleukin 2 receptor (CD25), for the treatment of moderately to severely active ulcerative colitis: a randomised, double blind, placebo controlled, dose ranging trial.Gut200655111568157410.1136/gut.2005.08985416603634
     [Google Scholar]
  80. ChisariC.G. SgarlataE. ArenaS. ToscanoS. LucaM. PattiF. Rituximab for the treatment of multiple sclerosis: a review.J. Neurol.2022269115918310.1007/s00415‑020‑10362‑z33416999
     [Google Scholar]
  81. LiZ. RichardsS. SurksH.K. JacobsA. PanzaraM.A. Clinical pharmacology of alemtuzumab, an anti-CD52 immunomodulator, in multiple sclerosis.Clin. Exp. Immunol.2018194329531410.1111/cei.1320830144037
     [Google Scholar]
  82. KwonY. LeeK.W. ParkH. SonJ.K. LeeJ. HongJ. ParkJ.B. KimS.J. Comparative study of human and cynomolgus T-cell depletion with rabbit anti-thymocyte globulin (rATG) treatment-for dose adjustment in a non-human primate kidney transplantation model.Am. J. Transl. Res.201911106422643231737194
     [Google Scholar]
  83. SamselR. Perioperative single high dose ATG-Fresenius S administration as induction immunosuppressive therapy in cadaveric renal transplantation--preliminary results.Ann Transplant.1999423739
     [Google Scholar]
  84. BirdP. BensenW. El-ZorkanyB. KaineJ. Manapat-ReyesB.H. Pascual-RamosV. WitcombeD. SomaK. ZhangR. ThirunavukkarasuK. Tofacitinib 5 mg twice daily in patients with rheumatoid arthritis and inadequate response to disease-modifying antirheumatic drugs.J. Clin. Rheumatol.201925311512610.1097/RHU.000000000000078629794874
     [Google Scholar]
  85. HuwilerA. Zangemeister-WittkeU. The sphingosine 1-phosphate receptor modulator fingolimod as a therapeutic agent: Recent findings and new perspectives.Pharmacol. Ther.2018185344910.1016/j.pharmthera.2017.11.00129127024
     [Google Scholar]
  86. QinS. TangX. ChenY. ChenK. FanN. XiaoW. ZhengQ. LiG. TengY. WuM. SongX. mRNA-based therapeutics: powerful and versatile tools to combat diseases.Signal Transduct. Target. Ther.20227116610.1038/s41392‑022‑01007‑w35597779
     [Google Scholar]
  87. StrzelecM. DetkaJ. MieszczakP. SobocińskaM.K. MajkaM. Immunomodulation—a general review of the current state-of-the-art and new therapeutic strategies for targeting the immune system.Front. Immunol.202314112770410.3389/fimmu.2023.112770436969193
     [Google Scholar]
  88. HosseinalizadehH. RabieeF. EghbalifardN. RajabiH. KlionskyD.J. RezaeeA. Regulating the regulatory T cells as cell therapies in autoimmunity and cancer.Front. Med. (Lausanne)202310124429810.3389/fmed.2023.124429837828948
     [Google Scholar]
  89. BluestoneJ.A. McKenzieB.S. BeilkeJ. RamsdellF. Opportunities for Treg cell therapy for the treatment of human disease.Front. Immunol.202314116613510.3389/fimmu.2023.116613537153574
     [Google Scholar]
  90. Charles A JanewayJ. TraversP. WalportM. ShlomchikM.J. The components of the immune system.2001Available from: https://www.healio.com/hematology-oncology/learn-immuno-oncology/the-immune-system/components-of-the-immune-system(accessed on 27-8-2024)
  91. ZhaoL. CaoY.J. EngineeredT. Engineered T cell therapy for cancer in the clinic.Front. Immunol.201910225010.3389/fimmu.2019.0225031681259
     [Google Scholar]
  92. XiaA.L. WangX.C. LuY.J. LuX.J. SunB. Chimeric-antigen receptor T (CAR-T) cell therapy for solid tumors: challenges and opportunities.Oncotarget2017852905219053110.18632/oncotarget.1936129163850
     [Google Scholar]
  93. TongC. LiangY. HanX. ZhangZ. ZhengX. WangS. SongB. Research progress of dendritic cell surface receptors and targeting.Biomedicines2023116167310.3390/biomedicines1106167337371768
     [Google Scholar]
  94. SabadoR.L. BhardwajN. Directing dendritic cell immunotherapy towards successful cancer treatment.Immunotherapy201021375610.2217/imt.09.4320473346
     [Google Scholar]
  95. HirayamaD. IidaT. NakaseH. The phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis.Int. J. Mol. Sci.20171919210.3390/ijms1901009229286292
     [Google Scholar]
  96. MantovaniA. AllavenaP. MarchesiF. GarlandaC. Macrophages as tools and targets in cancer therapy.Nat. Rev. Drug Discov.2022211179982010.1038/s41573‑022‑00520‑535974096
     [Google Scholar]
  97. AbelA.M. YangC. ThakarM.S. MalarkannanS. Natural killer cells: Development, maturation, and clinical utilization.Front. Immunol.20189186910.3389/fimmu.2018.0186930150991
     [Google Scholar]
  98. Immunomodulation C on ND in the S of AT. Promising Approaches to the Development of Immunomodulation for the Treatment of Infectious Diseases.2006
     [Google Scholar]
  99. SahinU. KarikóK. TüreciÖ. mRNA-based therapeutics — developing a new class of drugs.Nat. Rev. Drug Discov.2014131075978010.1038/nrd427825233993
     [Google Scholar]
  100. BeattyG.L. GladneyW.L. Immune escape mechanisms as a guide for cancer immunotherapy.Clin. Cancer Res.201521468769210.1158/1078‑0432.CCR‑14‑186025501578
     [Google Scholar]
  101. KhatunS. PuttaC.L. HakA. RenganA.K. Immunomodulatory nanosystems: An emerging strategy to combat viral infections.Biomaterials and Biosystems2023910007310.1016/j.bbiosy.2023.10007336967725
     [Google Scholar]
  102. Bascones-MartinezA. MattilaR. Gomez-FontR. MeurmanJ.H. Immunomodulatory drugs: Oral and systemic adverse effects.Med. Oral Patol. Oral Cir. Bucal2014191e24e3110.4317/medoral.1908723986016
     [Google Scholar]
  103. LinG. WangJ. YangY.G. ZhangY. SunT. Advances in dendritic cell targeting nano-delivery systems for induction of immune tolerance.Front. Bioeng. Biotechnol.202311124212610.3389/fbioe.2023.124212637877041
     [Google Scholar]
  104. TavakoliK. Pour-AboughadarehA. KianersiF. PoczaiP. EtminanA. ShooshtariL. Applications of CRISPR-Cas9 as an advanced genome editing system in life sciences.BioTech20211031410.3390/biotech1003001435822768
     [Google Scholar]
  105. WangD. MouH. LiS. LiY. HoughS. TranK. LiJ. YinH. AndersonD.G. SontheimerE.J. WengZ. GaoG. XueW. Adenovirus-mediated somatic genome editing of Pten by CRISPR/Cas9 in mouse liver in spite of Cas9-specific immune responses.Hum. Gene Ther.201526743244210.1089/hum.2015.08726086867
     [Google Scholar]
  106. AjinaR. ZamalinD. ZuoA. MoussaM. CatalfamoM. JablonskiS.A. WeinerL.M. SpCas9-expression by tumor cells can cause T cell-dependent tumor rejection in immunocompetent mice.OncoImmunology201985e157712710.1080/2162402X.2019.157712731069138
     [Google Scholar]
  107. CharlesworthC.T. DeshpandeP.S. DeverD.P. CamarenaJ. LemgartV.T. CromerM.K. VakulskasC.A. CollingwoodM.A. ZhangL. BodeN.M. BehlkeM.A. DejeneB. CieniewiczB. RomanoR. LeschB.J. Gomez-OspinaN. MantriS. Pavel-DinuM. WeinbergK.I. PorteusM.H. Identification of preexisting adaptive immunity to Cas9 proteins in humans.Nat. Med.201925224925410.1038/s41591‑018‑0326‑x30692695
     [Google Scholar]
  108. BoesenA. SundarK. CoicoR. Lassa fever virus peptides predicted by computational analysis induce epitope-specific cytotoxic-T- lymphocyte responses in HLA-A2.1 transgenic mice.Clin. Diagn. Lab. Immunol.200512101223123016210487
     [Google Scholar]
  109. KrzyszczykP. AcevedoA. DavidoffE.J. TimminsL.M. Marrero-BerriosI. PatelM. WhiteC. LoweC. SherbaJ.J. HartmanshennC. O’NeillK.M. BalterM.L. FritzZ.R. AndroulakisI.P. SchlossR.S. YarmushM.L. The growing role of precision and personalized medicine for cancer treatment.Technology (Singap.)2018603n047910010.1142/S233954781830002030713991
     [Google Scholar]
  110. GoswamiR. SubramanianG. SilayevaL. NewkirkI. DoctorD. ChawlaK. ChattopadhyayS. ChandraD. ChilukuriN. BetapudiV. Gene therapy leaves a vicious cycle.Front. Oncol.20199APR29710.3389/fonc.2019.0029731069169
     [Google Scholar]
  111. Al-TashiQ. SaadM.B. MuneerA. QureshiR. MirjaliliS. SheshadriA. LeX. VokesN.I. ZhangJ. WuJ. Machine learning models for the identification of prognostic and predictive cancer biomarkers: A systematic review.Int. J. Mol. Sci.2023249778110.3390/ijms2409778137175487
     [Google Scholar]
  112. KumarS.R.P. MarkusicD.M. BiswasM. HighK.A. HerzogR.W. Clinical development of gene therapy: results and lessons from recent successes.Mol. Ther. Methods Clin. Dev.201631603410.1038/mtm.2016.3427257611
     [Google Scholar]
  113. CastamanG. Di MinnoG. De CristofaroR. PeyvandiF. The arrival of gene therapy for patients with hemophilia A.Int. J. Mol. Sci.202223181022810.3390/ijms23181022836142153
     [Google Scholar]
  114. ChenG. WeiT. YangH. LiG. LiH. CRISPR-based therapeutic gene editing for duchenne muscular dystrophy: Advances, challenges and perspectives.Cells20221119296410.3390/cells1119296436230926
     [Google Scholar]
  115. LiuZ. ZhouZ. DangQ. XuH. LvJ. LiH. HanX. Immunosuppression in tumor immune microenvironment and its optimization from CAR-T cell therapy.Theranostics202212146273629010.7150/thno.7685436168626
     [Google Scholar]
  116. ZhouH. LiuD. LiangC. Challenges and strategies: The immune responses in gene therapy.Med. Res. Rev.200424674876110.1002/med.2000915250039
     [Google Scholar]
  117. RohnerE. YangR. FooK.S. GoedelA. ChienK.R. Unlocking the promise of mRNA therapeutics.Nat. Biotechnol.202240111586160010.1038/s41587‑022‑01491‑z36329321
     [Google Scholar]
  118. LiH. YangY. HongW. HuangM. WuM. ZhaoX. Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects.Signal Transduct. Target. Ther.20205112310.1038/s41392‑019‑0089‑y32296011
     [Google Scholar]
  119. GoetzL.H. SchorkN.J. Personalized medicine: motivation, challenges, and progress.Fertil. Steril.2018109695296310.1016/j.fertnstert.2018.05.00629935653
     [Google Scholar]
  120. ColellaP. RonzittiG. MingozziF. Emerging issues in AAV-mediated in vivo gene therapy.Mol. Ther. Methods Clin. Dev.201888710410.1016/j.omtm.2017.11.00729326962
     [Google Scholar]
  121. MitchellM.J. BillingsleyM.M. HaleyR.M. WechslerM.E. PeppasN.A. LangerR. Engineering precision nanoparticles for drug delivery.Nat. Rev. Drug Discov.202120210112410.1038/s41573‑020‑0090‑833277608
     [Google Scholar]
  122. RultenS.L. GroseR.P. GatzS.A. JonesJ.L. CameronA.J.M. The future of precision oncology.Int. J. Mol. Sci.202324161261310.3390/ijms24161261337628794
     [Google Scholar]
  123. PavlovicK. Tristán-ManzanoM. Maldonado-PérezN. Cortijo-GutierrezM. Sánchez-HernándezS. Justicia-LirioP. CarmonaM.D. HerreraC. MartinF. BenabdellahK. Using gene editing approaches to fine-tune the immune system.Front. Immunol.20201157067210.3389/fimmu.2020.57067233117361
     [Google Scholar]
  124. ElumalaiK. SrinivasanS. ShanmugamA. Review of the efficacy of nanoparticle-based drug delivery systems for cancer treatment.Biomed Technol2024510912210.1016/j.bmt.2023.09.001
     [Google Scholar]
  125. RittinerJ. CumaranM. MalhotraS. KantorB. Therapeutic modulation of gene expression in the disease state: Treatment strategies and approaches for the development of next-generation of the epigenetic drugs.Front. Bioeng. Biotechnol.202210103554310.3389/fbioe.2022.103554336324900
     [Google Scholar]
  126. ChoiE.H. SuhS. SearsA.E. HołubowiczR. KedharS.R. BrowneA.W. PalczewskiK. Genome editing in the treatment of ocular diseases.Exp. Mol. Med.20235581678169010.1038/s12276‑023‑01057‑237524870
     [Google Scholar]
  127. DunbarCE HighKA JoungJK KohnDB OzawaK SadelainM Gene therapy comes of age.Science20183596372eaan4672https://www.science.org/doi/abs/10.1126/science.aan4672
     [Google Scholar]
  128. MathurS SuttonJ Personalized medicine could transform healthcare.Biomed Rep20177135https://www.spandidos-publications.com/10.3892/br.2017.922?text=fulltext
     [Google Scholar]
  129. ToussaintJ GerardR On the mend: Revolutionizing healthcare to save lives and transform the industry.Lean Enterprise Institute, Cambridge, MA.2010
     [Google Scholar]
  130. PapanikolaouE BosioA The promise and the hope of gene therapy.Front Genome Editing20213618346https://www.frontiersin.org/journals/genome-editing/articles/10.3389/fgeed.2021.618346/full?ref=mackenziemorehead.com
     [Google Scholar]
  131. ChanchalDK ChaudharyJS KumarP AgnihotriN PorwalP CRISPR-based therapies: Revolutionizing drug development and precision medicine.Curr Gene Ther2024243193207https://www.ingentaconnect.com/content/ben/cgt/2024/00000024/00000003/art00003
     [Google Scholar]
  132. HopkinsC Javius-JonesK WangY HongH HuQ HongS Combinations of chemo-, immuno-, and gene therapies using nanocarriers as a multifunctional drug platform.Expert Opin Drug Delivery2022191013371349https://www.tandfonline.com/doi/abs/10.1080/17425247.2022.2112569
     [Google Scholar]
  133. SahuT RatreYK ChauhanS BhaskarLV NairMP VermaHK Nanotechnology based drug delivery system: Current strategies and emerging therapeutic potential for medical science.J Drug Deliv Sci Technol202163102487https://www.sciencedirect.com/science/article/abs/pii/S1773224721001672
     [Google Scholar]
  134. WangL WangFS GershwinME Human autoimmune diseases: A comprehensive update.J Intern Med20152784369395https://onlinelibrary.wiley.com/doi/full/10.1111/joim.12395
     [Google Scholar]
  135. LookM BandyopadhyayA BlumJS FahmyTM Application of nanotechnologies for improved immune response against infectious diseases in the developing world.Adv Drug Deliv Rev2010624-5378393https://www.sciencedirect.com/science/article/abs/pii/S0169409X09003524
     [Google Scholar]
/content/journals/cgt/10.2174/0115665232305409240918040639
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Immune Modulation Strategies in Gene Therapy: Overcoming Immune Barriers and Enhancing Efficacy
Curr. Gene Ther. 25, 374 (2025); https://doi.org/10.2174/0115665232305409240918040639
/content/journals/cgt/10.2174/0115665232305409240918040639
/content/journals/cgt/10.2174/0115665232305409240918040639
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  • Article Type:     Review Article
Keyword(s): gene delivery vectors; Gene therapy; immune checkpoints; immune modulation; immunomodulatory agents; immunotolerance

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