Due to the increased safety and efficiency of virus vectors, virus vector–mediated gene therapy is now widely used for various diseases, including monogenic diseases, complex disorders, and infectious diseases. Recent gene therapy trials have shown significant therapeutic benefits, and Chinese researchers have contributed significantly to this progress. This review highlights disease applications and strategies for virus vector–mediated gene therapy in preclinical studies and clinical trials in China.
Get full access to this article
View all access options for this article.
References
1.
Assessment of adenoviral vector safety and toxicity: report of the National Institutes of Health Recombinant DNA Advisory Committee. Hum Gene Ther, 2002; 13:3–13.
2.
KaiserJ. Gene therapy. Seeking the cause of induced leukemias in X-SCID trial. Science, 2003; 299:495.
3.
GinnSL, AlexanderIE, EdelsteinML, et al.Gene therapy clinical trials worldwide to 2012—an update. J Gene Med, 2013; 15:65–77.
4.
KottermanMA, ChalbergTW, SchafferDV. Viral vectors for gene therapy: translational and clinical outlook. Annu Rev Biomed Eng, 2015; 17:63–89.
5.
NaldiniL. Gene therapy returns to centre stage. Nature, 2015; 526:351–360.
6.
ChangJ, ZhaoX, WuX, et al.A Phase I study of KH901, a conditionally replicating granulocyte-macrophage colony-stimulating factor: armed oncolytic adenovirus for the treatment of head and neck cancers. Cancer Biol Ther, 2009; 8:676–682.
7.
YanC, YangM, LiZ, et al.Suppression of orthotopically implanted hepatocarcinoma in mice by umbilical cord-derived mesenchymal stem cells with sTRAIL gene expression driven by AFP promoter. Biomaterials, 2014; 35:3035–3043.
8.
BaiY, KanS, ZhouS, et al.Enhancement of the in vivo persistence and antitumor efficacy of CD19 chimeric antigen receptor T cells through the delivery of modified TERT mRNA. Cell Discov, 2015; 1:15040.
9.
HanX, ZhangY, XiongL, et al.Lentiviral-mediated netrin-1 overexpression improves motor and sensory functions in SCT rats associated with SYP and GAP-43 expressions. Mol Neurobiol, 2017; 54:1684–1697.
10.
LinH, HuH, DuanW, et al.Intramuscular delivery of scAAV9-hIGF1 prolongs survival in the hSOD1G93A ALS mouse model via upregulation of D-amino acid oxidase. Mol Neurobiol, 2016Dec19 [Epub ahead of print]; DOI:10.1007/s12035-016-0335-z.
11.
DingL, DongL, ChenX, et al.Increased expression of integrin-linked kinase attenuates left ventricular remodeling and improves cardiac function after myocardial infarction. Circulation, 2009; 120:764–773.
12.
ZhouQ, GuoR, WoodR, et al.Vascular endothelial growth factor C attenuates joint damage in chronic inflammatory arthritis by accelerating local lymphatic drainage in mice. Arthritis Rheum, 2011; 63:2318–2328.
13.
HuangP, ZhangL, GaoY, et al.Direct reprogramming of human fibroblasts to functional and expandable hepatocytes. Cell Stem Cell, 2014; 14:370–384.
14.
YeL, KanF, YanT, et al.Enhanced antiviral and antifibrotic effects of short hairpin RNAs targeting HBV and TGF-beta in HBV-persistent mice. Sci Rep, 2017; 7:3860.
15.
ThomasCE, EhrhardtA, KayMA. Progress and problems with the use of viral vectors for gene therapy. Nat Rev Genet, 2003; 4:346–358.
16.
SchambachA, MuellerD, GallaM, et al.Overcoming promoter competition in packaging cells improves production of self-inactivating retroviral vectors. Gene Ther, 2006; 13:1524–1533.
17.
YuSF, von RudenT, KantoffPW, et al.Self-inactivating retroviral vectors designed for transfer of whole genes into mammalian cells. Proc Natl Acad Sci U S A, 1986; 83:3194–3198.
18.
MaetzigT, GallaM, BaumC, et al.Gammaretroviral vectors: biology, technology and application. Viruses, 2011; 3:677–713.
19.
MontiniE, CesanaD, SchmidtM, et al.Hematopoietic stem cell gene transfer in a tumor-prone mouse model uncovers low genotoxicity of lentiviral vector integration. Nat Biotechnol, 2006; 24:687–696.
20.
Yanez-MunozRJ, BalagganKS, MacNeilA, et al.Effective gene therapy with nonintegrating lentiviral vectors. Nat Med, 2006; 12:348–353.
21.
BuchholzCJ, FriedelT, BuningH. Surface-engineered viral vectors for selective and cell type-specific gene delivery. Trends Biotechnol, 2015; 33:777–790.
22.
EhrhardtA, KayMA. A new adenoviral helper-dependent vector results in long-term therapeutic levels of human coagulation factor IX at low doses in vivo. Blood, 2002; 99:3923–3930.
23.
BischoffJR, KirnDH, WilliamsA, et al.An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science, 1996; 274:373–376.
24.
HeiseC, HermistonT, JohnsonL, et al.An adenovirus E1A mutant that demonstrates potent and selective systemic anti-tumoral efficacy. Nat Med, 2000; 6:1134–1139.
25.
YaroshOK, WandelerAI, GrahamFL, et al.Human adenovirus type 5 vectors expressing rabies glycoprotein. Vaccine, 1996; 14:1257–1264.
26.
BayerW, TenbuschM, LietzR, et al.Vaccination with an adenoviral vector that encodes and displays a retroviral antigen induces improved neutralizing antibody and CD4+ T-cell responses and confers enhanced protection. J Virol, 2010; 84:1967–1976.
27.
MingozziF, HighKA. Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges. Nat Rev Genet, 2011; 12:341–355.
28.
WuZ, AsokanA, SamulskiRJ. Adeno-associated virus serotypes: vector toolkit for human gene therapy. Mol Ther, 2006; 14:316–327.
NathwaniAC, GrayJT, NgCY, et al.Self-complementary adeno-associated virus vectors containing a novel liver-specific human factor IX expression cassette enable highly efficient transduction of murine and nonhuman primate liver. Blood, 2006; 107:2653–2661.
31.
HirschML, WolfSJ, SamulskiRJ. Delivering transgenic DNA exceeding the carrying capacity of AAV vectors. Methods Mol Biol, 2016; 1382:21–39.
32.
FinkDJ, GloriosoJC. Engineering herpes simplex virus vectors for gene transfer to neurons. Nat Med, 1997; 3:357–359.
33.
ManservigiR, ArgnaniR, MarconiP. HSV Recombinant vectors for gene therapy. Open Virol J, 2010; 4:123–156.
34.
ChenW, ZhengR, BaadePD, et al.Cancer statistics in China, 2015. CA Cancer J Clin, 2016; 66:115–132.
35.
BrennerMK, GottschalkS, LeenAM, et al.Is cancer gene therapy an empty suit?. Lancet Oncol, 2013; 14:e447–456.
36.
LiH, FuX, ChenY, et al.Use of adenovirus-delivered siRNA to target oncoprotein p28GANK in hepatocellular carcinoma. Gastroenterology, 2005; 128:2029–2041.
37.
KhuriFR, NemunaitisJ, GanlyI, et al.a controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer. Nat Med, 2000; 6:879–885.
XiaoT, FanJK, HuangHL, et al.VEGI-armed oncolytic adenovirus inhibits tumor neovascularization and directly induces mitochondria-mediated cancer cell apoptosis. Cell Res, 2010; 20:367–378.
40.
RosenbergSA, RestifoNP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science, 2015; 348:62–68.
41.
KochenderferJN, WilsonWH, JanikJE, et al.Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood, 2010; 116:4099–4102.
42.
KochenderferJN, DudleyME, KassimSH, et al.Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol, 2015; 33:540–549.
43.
RosenbergSA. Cell transfer immunotherapy for metastatic solid cancer—what clinicians need to know. Nat Rev Clin Oncol, 2011; 8:577–585.
44.
YuanX, ZhangQ, LiZ, et al.Mesenchymal stem cells deliver and release conditionally replicative adenovirus depending on hepatic differentiation to eliminate hepatocellular carcinoma cells specifically. Cancer Lett, 2016; 381:85–95.
45.
LvF, QiuY, ZhangY, et al.Adeno-associated virus-mediated anti-DR5 chimeric antibody expression suppresses human tumor growth in nude mice. Cancer Lett, 2011; 302:119–127.
46.
CaoL, LiuL, ChenZY, et al.Olfactory ensheathing cells genetically modified to secrete GDNF to promote spinal cord repair. Brain, 2004; 127:535–549.
47.
WuHF, CenJS, ZhongQ, et al.The promotion of functional recovery and nerve regeneration after spinal cord injury by lentiviral vectors encoding Lingo-1 shRNA delivered by Pluronic F-127. Biomaterials, 2013; 34:1686–1700.
48.
CanterRG, PenneyJ, TsaiLH. The road to restoring neural circuits for the treatment of Alzheimer's disease. Nature, 2016; 539:187–196.
49.
SnyderEM, NongY, AlmeidaCG, et al.Regulation of NMDA receptor trafficking by amyloid-beta. Nat Neurosci, 2005; 8:1051–1058.
50.
HuR, WeiP, JinL, et al.Overexpression of EphB2 in hippocampus rescues impaired NMDA receptors trafficking and cognitive dysfunction in Alzheimer model. Cell Death Dis, 2017; 8:e2717.
51.
ShirayamaY, ChenAC, NakagawaS, et al.Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. J Neurosci, 2002; 22:3251–3261.
52.
MaXC, LiuP, ZhangXL, et al.Intranasal delivery of recombinant AAV containing BDNF fused with HA2TAT: a potential promising therapy strategy for major depressive disorder. Sci Rep, 2016; 6:22404.
53.
LeeSP, YounSW, ChoHJ, et al.Integrin-linked kinase, a hypoxia-responsive molecule, controls postnatal vasculogenesis by recruitment of endothelial progenitor cells to ischemic tissue. Circulation, 2006; 114:150–159.
54.
BolliR. Oxygen-derived free radicals and myocardial reperfusion injury: an overview. Cardiovasc Drugs Ther, 1991; 5:249–268.
55.
PanQ, QinX, MaS, et al.Myocardial protective effect of extracellular superoxide dismutase gene modified bone marrow mesenchymal stromal cells on infarcted mice hearts. Theranostics, 2014; 4:475–486.
56.
ShimamuraM, NakagamiH, KoriyamaH, et al.Gene therapy and cell-based therapies for therapeutic angiogenesis in peripheral artery disease. Biomed Res Int, 2013; 2013:186215.
57.
LiuLZ, LiC, ChenQ, et al.MiR-21 induced angiogenesis through AKT and ERK activation and HIF-1alpha expression. PLoS One, 2011; 6:e19139.
58.
ZhouY, ZhuY, ZhangL, et al.Human stem cells overexpressing miR-21 promote angiogenesis in critical limb ischemia by targeting CHIP to enhance HIF-1alpha activity. Stem Cells, 2016; 34:924–934.
59.
ZhangF, ChenCL, QianJQ, et al.Long-term modifications of blood pressure in normotensive and spontaneously hypertensive rats by gene delivery of rAAV-mediated cytochrome P450 arachidonic acid hydroxylase. Cell Res, 2005; 15:717–724.
60.
GelbandCH, KatovichMJ, RaizadaMK. Current perspectives on the use of gene therapy for hypertension. Circ Res, 2000; 87:1118–1122.
61.
MeasePJ, WeiN, FudmanEJ, et al.Safety, tolerability, and clinical outcomes after intraarticular injection of a recombinant adeno-associated vector containing a tumor necrosis factor antagonist gene: results of a Phase 1/2 Study. J Rheumatol, 2010; 37:692–703.
62.
Lai Kwan LamQ, King Hung KoO, ZhengBJ, et al.Local BAFF gene silencing suppresses Th17-cell generation and ameliorates autoimmune arthritis. Proc Natl Acad Sci U S A, 2008; 105:14993–14998.
63.
ShiJ, DiaoZ, ZhouJ, et al.Epirubicin potentiates recombinant adeno-associated virus type 2/5-mediated TRAIL expression in fibroblast-like synoviocytes and augments the antiarthritic effects of rAAV2/5-TRAIL. Arthritis Rheum, 2012; 64:1345–1354.
64.
GaoJ, QinZ, GuanX, et al.Overexpression of GSN could decrease inflammation and apoptosis in EAE and may enhance vitamin D therapy on EAE/MS. Sci Rep, 2017; 7:604.
65.
WangFS, FanJG, ZhangZ, et al.The global burden of liver disease: the major impact of China. Hepatology, 2014; 60:2099–2108.
66.
RezvaniM, Espanol-SunerR, MalatoY, et al.In vivo hepatic reprogramming of myofibroblasts with AAV vectors as a therapeutic strategy for liver fibrosis. Cell Stem Cell, 2016; 18:809–816.
67.
SongG, PacherM, BalakrishnanA, et al.Direct reprogramming of hepatic myofibroblasts into hepatocytes in vivo attenuates liver fibrosis. Cell Stem Cell, 2016; 18:797–808.
68.
LiuJ, HuX, ChenJ, et al.Pericentral hepatocytes produce insulin-like growth factor-2 to promote liver regeneration during selected injuries in mice. Hepatology, 2017; 66:2002–2015.
69.
ParvizF, MatulloC, GarrisonWD, et al.Hepatocyte nuclear factor 4alpha controls the development of a hepatic epithelium and liver morphogenesis. Nat Genet, 2003; 34:292–296.
70.
YueHY, YinC, HouJL, et al.Hepatocyte nuclear factor 4alpha attenuates hepatic fibrosis in rats. Gut, 2010; 59:236–246.
71.
WangPX, JiYX, ZhangXJ, et al.Targeting CASP8 and FADD-like apoptosis regulator ameliorates nonalcoholic steatohepatitis in mice and nonhuman primates. Nat Med, 2017; 23:439–449.
72.
ChenG, BlockJM, EvansAA, et al.Gateway to Care campaign: a public health initiative to reduce the burden of hepatitis B in Haimen City, China. BMC Public Health, 2014; 14:754.
73.
PetersenJ, ThompsonAJ, LevreroM. Aiming for cure in HBV and HDV infection. J Hepatol, 2016; 65:835–848.
74.
ShihYM, SunCP, ChouHH, et al.Combinatorial RNA interference therapy prevents selection of pre-existing HBV variants in human liver chimeric mice. Sci Rep, 2015; 5:15259.
LiuL, HaoY, LuoZ, et al.Broad HIV-1 neutralizing antibody response induced by heterologous gp140/gp145 DNA prime-vaccinia boost immunization. Vaccine, 2012; 30:4135–4143.
77.
BlaeseRM, CulverKW, MillerAD, et al.T lymphocyte-directed gene therapy for ADA-SCID: initial trial results after 4 years. Science, 1995; 270:475–480.
78.
The ADA human gene therapy clinical protocol. Hum Gene Ther. 1990; 1:327–362.
79.
QiuX, LuD, ZhouJ, et al.Implantation of autologous skin fibroblast genetically modified to secrete clotting factor IX partially corrects the hemorrhagic tendencies in two hemophilia B patients. Chin Med J (Engl), 1996; 109:832–839.
80.
WanX, PeiH, ZhaoMJ, et al.Efficacy and safety of rAAV2-ND4 treatment for Leber's hereditary optic neuropathy. Sci Rep, 2016; 6:21587.
81.
CartierN, AubourgP. Hematopoietic stem cell transplantation and hematopoietic stem cell gene therapy in X-linked adrenoleukodystrophy. Brain Pathol, 2010; 20:857–862.
Cavazzana-CalvoM, PayenE, NegreO, et al.Transfusion independence and HMGA2 activation after gene therapy of human beta-thalassaemia. Nature, 2010; 467:318–322.
84.
CaoY, LiS, LiHL, et al.[Clinical tolerance trial on recombinant human endostatin adenovirus]. Ai Zheng, 2007; 26:856–860.
85.
ChenCB, PanJJ, XuLY. [Recombinant adenovirus p53 agent injection combined with radiotherapy in treatment of nasopharyngeal carcinoma: a Phase II clinical trial]. Zhonghua Yi Xue Za Zhi, 2003; 83:2033–2035.
86.
DiL, ZhuY, JiaJ, et al.Clinical safety of induced CTL infusion through recombinant adeno-associated virus-transfected dendritic cell vaccination in Chinese cancer patients. Clin Transl Oncol, 2012; 14:675–681.
87.
DongJ, LiW, DongA, et al.Gene therapy for unresectable hepatocellular carcinoma using recombinant human adenovirus type 5. Med Oncol, 2014; 31:95.
88.
DongM, LiX, HongLJ, et al.Advanced malignant pleural or peritoneal effusion in patients treated with recombinant adenovirus p53 injection plus cisplatin. J Int Med Res, 2008; 36:1273–1278.
89.
GaoYD, ChenGL, GuoPD, et al.[Study on the application effect of Once Vex(GM)(-)(CSF) and adriamycin in the interventional therapy of malignant tumor in clinical curative effect]. Zhonghua Yi Xue Za Zhi, 2016; 96:2173–2175.
90.
GuanYS, LiuY, HeQ, et al.p53 gene therapy in combination with transcatheter arterial chemoembolization for HCC: one-year follow-up. World J Gastroenterol, 2011; 17:2143–2149.
91.
GuanYS, LiuY, ZouQ, et al.Adenovirus-mediated wild-type p53 gene transfer in combination with bronchial arterial infusion for treatment of advanced non-small-cell lung cancer, one year follow-up. J Zhejiang Univ Sci B, 2009; 10:331–340.
92.
HanDM, HuangZG, ZhangW, et al.[Effectiveness of recombinant adenovirus p53 injection on laryngeal cancer: Phase I clinical trial and follow up]. Zhonghua Yi Xue Za Zhi, 2003; 83:2029–2032.
93.
LiY, LiLJ, WangLJ, et al.Selective intra-arterial infusion of rAd-p53 with chemotherapy for advanced oral cancer: a randomized clinical trial. BMC Med, 2014; 12:16.
94.
LiY, LiLJ, ZhangST, et al.In vitro and clinical studies of gene therapy with recombinant human adenovirus-p53 injection for oral leukoplakia. Clin Cancer Res, 2009; 15:6724–6731.
95.
LinX, HuangH, LiS, et al.A Phase I clinical trial of an adenovirus-mediated endostatin gene (E10A) in patients with solid tumors. Cancer Biol Ther, 2007; 6:648–653.
96.
LiuS, ChenP, HuM, et al.Randomized, controlled PII study of post-surgery radiotherapy combined with recombinant adenoviral human p53 gene therapy in treatment of oral cancer. Cancer Gene Ther, 2013; 20:375–378.
97.
LuP, YangX, HuangY, et al.Antitumor activity of a combination of rAd2p53 adenoviral gene therapy and radiotherapy in esophageal carcinoma. Cell Biochem Biophys, 2011; 59:147–152.
98.
LuW, ZhengS, LiXF, et al.Intra-tumor injection of H101, a recombinant adenovirus, in combination with chemotherapy in patients with advanced cancers: a pilot Phase II clinical trial. World J Gastroenterol, 2004; 10:3634–3638.
99.
MaWS, MaJG, XingLN. Efficacy and safety of recombinant human adenovirus p53 combined with chemoradiotherapy in the treatment of recurrent nasopharyngeal carcinoma. Anticancer Drugs, 2017; 28:230–236.
100.
NingX, SunZ, WangY, et al.Docetaxel plus trans-tracheal injection of adenoviral-mediated p53 versus docetaxel alone in patients with previously treated non-small-cell lung cancer. Cancer Gene Ther, 2011; 18:444–449.
101.
SuX, ChenWJ, XiaoSW, et al.Effect and safety of recombinant adenovirus-p53 transfer combined with radiotherapy on long-term survival of locally advanced cervical cancer. Hum Gene Ther, 2016; 27:1008–1014.
102.
TianG, LiuJ, ZhouJS, et al.Multiple hepatic arterial injections of recombinant adenovirus p53 and 5-fluorouracil after transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: a pilot Phase II trial. Anticancer Drugs, 2009; 20:389–395.
103.
XiaZJ, ChangJH, ZhangL, et al.[Phase III randomized clinical trial of intratumoral injection of E1B gene-deleted adenovirus (H101) combined with cisplatin-based chemotherapy in treating squamous cell cancer of head and neck or esophagus]. Ai Zheng, 2004; 23:1666–1670.
104.
XuF, LiS, LiXL, et al.Phase I and biodistribution study of recombinant adenovirus vector-mediated herpes simplex virus thymidine kinase gene and ganciclovir administration in patients with head and neck cancer and other malignant tumors. Cancer Gene Ther, 2009; 16:723–730.
105.
XuRH, YuanZY, GuanZZ, et al.[Phase II clinical study of intratumoral H101, an E1B deleted adenovirus, in combination with chemotherapy in patients with cancer]. Ai Zheng, 2003; 22:1307–1310.
106.
YangZX, WangD, WangG, et al.Clinical study of recombinant adenovirus-p53 combined with fractionated stereotactic radiotherapy for hepatocellular carcinoma. J Cancer Res Clin Oncol, 2010; 136:625–630.
107.
ZhangS, LiY, LiL, et al.Phase I study of repeated intraepithelial delivery of adenoviral p53 in patients with dysplastic oral leukoplakia. J Oral Maxillofac Surg, 2009; 67:1074–1082.
108.
ZhangS, XuG, LiuC, et al.Clinical study of recombinant adenovirus-p53 (Adp53) combined with hyperthermia in advanced cancer (a report of 15 cases). Int J Hyperthermia, 2005; 21:631–636.
109.
ZhangSW, XiaoSW, LiuCQ, et al.[Treatment of head and neck squamous cell carcinoma by recombinant adenovirus-p53 combined with radiotherapy: a Phase II clinical trial of 42 cases]. Zhonghua Yi Xue Za Zhi, 2003; 83:2023–2028.
110.
ZhangSW, XiaoSW, LiuCQ, et al.[Recombinant adenovirus-p53 gene therapy combined with radiotherapy for head and neck squamous-cell carcinoma]. Zhonghua Zhong Liu Za Zhi, 2005; 27:426–428.
111.
ZhaoWZ, WangJK, LiW, et al.[Clinical research on recombinant human Ad-p53 injection combined with cisplatin in treatment of malignant pleural effusion induced by lung cancer]. Ai Zheng, 2009; 28:1324–1327.
112.
ZhouJ, ZhangY, ZhaoG, et al.[The preliminary study of recombinant adenovirus p53 combined with transarterial embolization with particles for advanced hepatocellular carcinoma]. Zhonghua Yi Xue Za Zhi, 2014; 94:660–663.
113.
ZhuJX, LiZM, GengFY, et al.[Treatment of recurrent malignant gliomas by surgery combined with recombinant adenovirus-p53 injection]. Zhonghua Zhong Liu Za Zhi, 2010; 32:709–712.
114.
LiN, ZhouJ, WengD, et al.Adjuvant adenovirus-mediated delivery of herpes simplex virus thymidine kinase administration improves outcome of liver transplantation in patients with advanced hepatocellular carcinoma. Clin Cancer Res, 2007; 13:5847–5854.
115.
NormileD. China sprints ahead in CRISPR therapy race. Science, 2017; 358:20–21.
116.
LinY, WanJQ, GaoGY, et al.Direct hippocampal injection of pseudo lentivirus-delivered nerve growth factor gene rescues the damaged cognitive function after traumatic brain injury in the rat. Biomaterials, 2015; 69:148–157.
117.
LiuR, ZhaoW, ZhaoQ, et al.Endoplasmic reticulum protein 29 protects cortical neurons from apoptosis and promoting corticospinal tract regeneration to improve neural behavior via caspase and Erk signal in rats with spinal cord transection. Mol Neurobiol, 2014; 50:1035–1048.
118.
ZhangX, ShiLL, GaoX, et al.Lentivirus-mediated inhibition of tumour necrosis factor-alpha improves motor function associated with PRDX6 in spinal cord contusion rats. Sci Rep, 2015; 5:8486.
119.
WangCY, WangZY, XieJW, et al.CD36 upregulation mediated by intranasal LV-NRF2 treatment mitigates hypoxia-induced progression of Alzheimer's-like pathogenesis. Antioxid Redox Signal, 2014; 21:2208–2230.
120.
ChenL, GaoB, FangM, et al.Lentiviral vector-induced overexpression of RGMa in the hippocampus suppresses seizures and mossy fiber sprouting. Mol Neurobiol, 2017; 54:1379–1391.
121.
FanL, LinC, ZhuoS, et al.Transplantation with survivin-engineered mesenchymal stem cells results in better prognosis in a rat model of myocardial infarction. Eur J Heart Fail, 2009; 11:1023–1030.
122.
ZhaoXY, HuSJ, LiJ, et al.rAAV-asPLB transfer attenuates abnormal sarcoplasmic reticulum Ca2+-ATPase activity and cardiac dysfunction in rats with myocardial infarction. Eur J Heart Fail, 2008; 10:47–54.
123.
LuD, ZhangL, WangH, et al.Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) enhances engraftment and angiogenesis of mesenchymal stem cells in diabetic hindlimb ischemia. Diabetes, 2012; 61:1153–1159.
124.
LiuZ, GouY, ZhangH, et al.Estradiol improves cardiovascular function through up-regulation of SOD2 on vascular wall. Redox Biol, 2014; 3:88–99.
125.
TsuiTY, LauCK, MaJ, et al.rAAV-mediated stable expression of heme oxygenase-1 in stellate cells: a new approach to attenuate liver fibrosis in rats. Hepatology, 2005; 42:335–342.
126.
ZhaoGN, ZhangP, GongJ, et al.Tmbim1 is a multivesicular body regulator that protects against non-alcoholic fatty liver disease in mice and monkeys by targeting the lysosomal degradation of Tlr4. Nat Med, 2017; 23:742–752.
127.
ZouD, ZhangZ, YeD, et al.Repair of critical-sized rat calvarial defects using genetically engineered bone marrow–derived mesenchymal stem cells overexpressing hypoxia-inducible factor-1alpha. Stem Cells, 2011; 29:1380–1390.
128.
TangJB, WuYF, CaoY, et al.Basic FGF or VEGF gene therapy corrects insufficiency in the intrinsic healing capacity of tendons. Sci Rep, 2016; 6:20643.
