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Stem cell gene therapy: the risks of insertional mutagenesis and approaches to minimize genotoxicity

Chuanfeng Wu, Cynthia E. Dunbar

《医学前沿（英文）》 2011年 第5卷 第4期   页码 356-371 doi: 10.1007/s11684-011-0159-1

摘要： Virus-based vectors are widely used in hematopoietic stem cell (HSC) gene therapy, and have the ability to integrate permanently into genomic DNA, thus driving long-term expression of corrective genes in all hematopoietic lineages. To date, HSC gene therapy has been successfully employed in the clinic for improving clinical outcomes in small numbers of patients with X-linked severe combined immunodeficiency (SCID-X1), adenosine deaminase deficiency (ADA-SCID), adrenoleukodystrophy (ALD), thalassemia, chronic granulomatous disease (CGD), and Wiskott-Aldrich syndrome (WAS). However, adverse events were observed during some of these HSC gene therapy clinical trials, linked to insertional activation of proto-oncogenes by integrated proviral vectors leading to clonal expansion and eventual development of leukemia. Numerous studies have been performed to understand the molecular basis of vector-mediated genotoxicity, with the aim of developing safer vectors and lower-risk gene therapy protocols. This review will summarize current information on the mechanisms of insertional mutagenesis in hematopoietic stem and progenitor cells due to integrating gene transfer vectors, discuss the available assays for predicting genotoxicity and mapping vector integration sites, and introduce newly-developed approaches for minimizing genotoxicity as a way to further move HSC gene therapy forward into broader clinical application.

关键词： gene therapy     hematopoietic stem cells     insertional mutagenesis     genotoxicity     induced pluripotent stem cell    

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Optimized human factor IX expression cassettes for hepatic-directed gene therapy of hemophilia B

null

《医学前沿（英文）》 2015年 第9卷 第1期   页码 90-99 doi: 10.1007/s11684-015-0390-2

摘要：

Gene therapy provides a potential cure for hemophilia B, and significant progress has been achieved in liver-directed gene transfer mediated by adeno-associated viral vectors. Recent clinical trials involving the use of a self-complementary adeno-associated virus serotype 8-human codon-optimized factor IX (AAV8-hFIXco) vector demonstrated encouraging efficacy with hFIX expression stabilized at 1% to 6% of normal level in patients, but safety concerns related to high vector doses are still present. Thus, further improvement of AAV vectors and hFIX expression cassette may positively contribute to the ultimate success of hemophilia B gene therapy. In this study, to obtain a higher expression level of hFIX that potentiates the coagulant capacity of recipients, human FIX expression vector was optimized by upgrading the codon adaption index and adjusting the GC content, inserting a Kozak sequence (GCCACC), and introducing a gain-of-function mutation, R338L (FIX Padua). The efficiency of the published and the presently constructed cassettes was compared through in vivo screening. In addition, the regulatory elements that control the FIX gene expression in these cassettes were screened for liver-specific effectiveness. Among all the constructed cassettes, scAAV-Pre-hFIXco-SIH-R338L, which was the construct under the control of the prothrombin enhancer and prealbumin promoter, resulted in the highest level of coagulant activity, and the expression levels of two constructed cassettes (scAAV-Chi-hFIXco-SIH-R338L and scAAV-Pre-hFIXco-SIH-R338L) were also higher than that of the published cassette (scAAV-LP1-hFIXco-SJ). In summary, our strategies led to a substantial increase in hFIX expression at the protein level or a remarkably elevated coagulant activity. Thus, these reconstructs of hFIX with AAV vector may potentially contribute to the creation of an efficacious gene therapy of hemophilia B.

关键词： factor IX     hemophilia B     liver-specific regulatory elements     hydrodynamic gene transfer    

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Gene therapy for hemophilia B mice with scAAV8-LP1-hFIX

null

《医学前沿（英文）》 2016年 第10卷 第2期   页码 212-218 doi: 10.1007/s11684-016-0438-y

摘要：

Hemophilia B is a hemorrhagic disease caused by the deficiency of clotting factor IX (FIX). Gene therapy might be the ultimate strategy for the disease. However, two main problems that should be solved in gene therapy for hemophilia B are immunity and safety. Self-complementary adeno-associated virus serotype 8 (scAAV8), a non-human primate AAV featuring low immunogenicity and high transfection efficiency in liver cells, might be a potential vector for hemophilia B gene therapy. A strong liver-specific promoter-1 (LP1) was inserted and mutant human FIX Arg338Ala was introduced into plasmid scAAV8-LP1 to develop an optimized AAV8 vector that expresses human clotting factor FIX (hFIX). The efficiency of scAAV8-LP1-hFIX administered through normal systemic injection or hydrodynamic injection was compared. A high expression was achieved using hydrodynamic injection, and the peak hFIX expression levels in the 5×1011 and 1×1011 virus genome (vg) cohorts were 31.94% and 25.02% of normal level, respectively, at 60 days post-injection. From the perspective of long-term (200 days) expression, both injection methods presented promising results with the concentration value maintained above 4% of normal plasma. The results were further verified by enzyme-linked immunosorbent assay and activated partial thromboplastin time. Our study provides a potential gene therapy method for hemophilia B.

关键词： hemophilia B     AAV8     hFIX     gene therapy    

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Molecular engineering of dendrimer nanovectors for siRNA delivery and gene silencing

Yu Cao, Xiaoxuan Liu, Ling Peng

《化学科学与工程前沿（英文）》 2017年 第11卷 第4期   页码 663-675 doi: 10.1007/s11705-017-1623-5

摘要： Small interfering RNA (siRNA) therapeutics hold great promise to treat a variety of diseases, as long as they can be delivered safely and effectively into cells. Dendrimers are appealing vectors for siRNA delivery by virtue of their well-defined molecular architecture and multivalent cooperativity. However, the clinical translation of RNA therapeutics mediated by dendrimer delivery is hampered by the lack of dendrimers that are of high quality to meet good manufacturing practice standard. In this context, we have developed small amphiphilic dendrimers that self-assemble into supramolecular structures, which mimic high-generation dendrimers synthesized with covalent construction, yet are easy to produce in large amount and superior quality. Indeed, the concept of supramolecular dendrimers has proved to be very promising, and has opened up a new avenue for dendrimer-mediated siRNA delivery. A series of self-assembling supramolecular dendrimers have consequently been established, some of them out-performing the currently available nonviral vectors in delivering siRNA to various cell types and , including human primary cells and stem cells. This short review presents a brief introduction to RNAi therapeutics, the obstacles to their delivery and the advantages of dendrimer delivery vectors as well as our bio-inspired structurally flexible dendrimers for siRNA delivery. We then highlight our efforts in creating self-assembling amphiphilic dendrimers to construct supramolecular dendrimer nanosystems for effective siRNA delivery as well as the related structural alterations to enhance delivery efficiency. The advent of self-assembling supramolecular dendrimer nanovectors holds great promise and heralds a new era of dendrimer-mediated delivery of RNA therapeutics in biomedical applications.

关键词： gene therapy     RNAi therapeutics     dendrimer     nanovectors     gene silencing    

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Investigation of gene therapy of denovirus in immune suppression

XIA Xi, WANG Beibei, CAO Li, CHEN Gang, WU Peng, LU Yunping, ZHOU Jianfeng, MA Ding

《医学前沿（英文）》 2008年 第2卷 第4期   页码 386-390 doi: 10.1007/s11684-008-0074-2

摘要： The aim of this paper is to investigate the safety of reconstructed adenovirus in immunosuppressive therapeutics and to explore the role of ciclosporin A in antagonizing the elimination of the vector. Several rats were given retroperitoneal injection of purified ADV-TK in order to obtain models. After 14 days’ treatment of ciclosporin A, samples of different periods were obtained, then stained with hematoxylin-eosin (HE) to detect inflammation reactions. Immunohistochemistry was used to examine the expression of adenovirus in organs. The results are as follows: (1) In HE stained sections of the organs, some transitory and reversible inflammation was detected. (2) In immunohistochemistry assay, reconstructed adenovirus decreased gradually as time went by in the control group, while it did not happen in the experimental group in which the adenovirus showed a relative increase compared with their counterparts ( < 0.05). (3) The distributions of adenovirus in the liver, spleen and lung were higher than those in the other organs detected. Reconstructed adenovirus as a vector is definitely safe in immunosuppressive therapeutics, and ciclosporin A, to some extent, is able to consequently inhibit the immune response of the rats and prolong the existing period of adenovirus.

关键词： different     reversible inflammation     immunohistochemistry     reconstructed adenovirus     ciclosporin    

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Construction of lentiviral vector carrying Rab9 gene and its expression in mouse brain

Youguo HAO, Min ZHANG, Jinzhi XU, Bitao BU, Jiajun WEI

《医学前沿（英文）》 2009年 第3卷 第2期   页码 141-147 doi: 10.1007/s11684-009-0041-6

摘要： Rab proteins and their effectors facilitate vesicular transport by tethering donor vesicles to their respective target membranes. Rab9 mediates late endosome-to- -Golgi-network trafficking. To explore the possibility of Rab9-related gene therapy for neurodegenerative diseases, we packed Lentivirus encoding Rab9. The expressing plasmid pCDH1-MCF1-Rab9-EF1-copGFP was constructed by using molecular biological techniques. The Lentivirus encoding Rab9 cDNA was packed by Lifectamine-2000 mediated co-transfection of the plasmid pPACKH1- , pPACKH1- and pVSV- into 293T cells. DNA sequencing proved the successful construction of pCDH1-MCF1-Rab9-EF1-copGFP. After 72 hours, the expression of GFP could be detected in BV-2 cells. Western blotting revealed that the Rab9 gene expression in BALB/c mice brain was up-regulated significantly 4 weeks after injection with Lentivirus encoding Rab9, which evidenced a satisfactory increasing effect of this virus. Administration of Lenti-Rab9 to postnatal day 3 Niemann-Pick disease type C (NPC) mice reduced motor defects and prevented the weight loss associated with female NPC mice, as well as modulating the death rate of Purkinje neurons. It is concluded that the packaging of Lentivirus encoding Rab9 was successful. Lentivirus encoding Rab9 can increase the expression of Rab9 gene effectively, which might offer a novel means for the treatment of neurodegenerative diseases.

关键词： Rab9     lentivirus     gene therapy     gene transfer    

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Adenovirus-mediated antisense ERK2 gene therapy ameliorates chronic allograft nephropathy in a rat model

Zhao DING, Zhishui CHEN, Xilin CHEN, Ming CAI, Hui GUO, Nianqiao GONG

《医学前沿（英文）》 2009年 第3卷 第2期   页码 204-210 doi: 10.1007/s11684-009-0039-0

摘要： To investigate the effect and underlying mechanism of adenovirus-mediated antisense ERK2 (Adanti-ERK2) gene therapy upon chronic allograft nephropathy (CAN) of rats, male Lewis (LEW, RT11) rats received male Fisher (F344, RT11v1) renal allografts. The recipients were divided into three groups: (1) empty control group; (2) vector control group; (3) gene therapy group. All recipients were sacrificed for the grafts and serum analysis at the 24th week after transplantation. Morphometric analysis was used to determine the fibrosis of grafts. Immunohistochemistry was used to detect the expression of E-Cadherin, Vimentin, TβR I and the infiltration of CD4 T lymphocyte, CD8 T lymphocyte and ED-1 monocytes. Enzyme linked immunosorbent assay (ELISA) was used to detect TGF-β1 in serum. The grafts in the control group and vector control group showed CAN. There was less E-Cadherin in renal tubular epithelial cells in the empty control group but more Vimentin and TβR I. In the gene therapy group, the fibrosis was ameliorated and fewer T lymphocytes and ED-1 monocytes infiltrated in the interstitium. There was no significant difference in the expression of E-Cadherin between the gene therapy group and normal rats. Compared with the empty control group, the expression of TGF-β1 in the gene therapy group was down-regulated. Adanti-ERK2 gene therapy protects the renal allograft and attenuates graft fibrosis, which may be correlated with a decreased renal tubular epithelial mesenchymal transition, a decreased infiltration of CD4 T lymphocyte, CD8 T lymphocytes and ED-1 monocytes in renal interstitium, and the down-regulated TGF-β1 expression.

关键词： anti-ERK2     renal transplantation     epithelial mesenchymal transition     chronic allograft nephropathy    

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Antitumor immunity of human SART3 gene vaccine against mouse tumor

HE Yu, YANG Shuhua, LIU Yong, LI Tao

《医学前沿（英文）》 2008年 第2卷 第1期   页码 51-57 doi: 10.1007/s11684-008-0010-5

摘要： To determine whether squamous cell carcinoma antigen recognized by human T cell 3 (SART3) gene can induce antitumor immunity against tumor cells which express the gene, we constructed mouse tumor cells expressing human SART3 (LM8-SART3) and carried out experiments . After subcutaneous injection with SART3 gene vaccine, cytotoxic T lymphocyte (CTL) activity was measured using Cell Counting Kit-8. As for the part, C3H mice were divided into several groups. One group was challenged with tumor cells after immunity. Another group was treated with the vaccine after tumor implantation. It was found that human SART3 DNA vaccine can elicit a specific CTL reaction from the mouse splenocytes. After vaccination, tumor occurrence and tumor growth speed was reduced. The vaccine also shows activity in tumor treatment. We conclude that the human SART3 DNA vaccine can induce antitumor ability against tumor cells expressing human SART3 (LM8-SART3) which may provide new possibilities in antitumor therapy.

关键词： antitumor therapy     occurrence     implantation     DNA vaccine     SART3 DNA    

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NES1/KLK10 and hNIS gene therapy enhanced iodine-131 internal radiation in PC3 proliferation

Jiajia Hu, Wenbin Shen, Qian Qu, Xiaochun Fei, Ying Miao, Xinyun Huang, Jiajun Liu, Yingli Wu, Biao Li

《医学前沿（英文）》 2019年 第13卷 第6期   页码 646-657 doi: 10.1007/s11684-018-0643-y

摘要： gene is thought to be a tumor-suppressor gene. Our previous study found that overexpression of gene in PC3 cell line could slow down the tumor proliferation rate, associated with a mild decrease in expression. The decrease could increase the sensitivity of radiotherapy to tumors. Thus, we supposed to have an “enhanced firepower” effect by combining overexpressed gene therapy and I radiation therapy uptake by overexpressed hNIS protein. We found a weak endogenous expression of hNIS protein in PC3 cells and demonstrated that the low expression of hNIS protein in PC3 cells might be the reason for the low iodine uptake. By overexpressing in PC3, the radioactive iodine uptake ability was significantly increased. Results of and tumor proliferation experiments and F-fluorothymidine ( F-FLT) micro-positron emission tomography/computed tomography (micro-PET/CT) imaging showed that the combined gene therapy and I radiation therapy mediated by overexpressed hNIS protein had the best tumor proliferative inhibition effect. Immunohistochemistry showed an obvious decrease of expression and the lowest expression. These data suggest that via inhibition of expression, overexpressed might enhance the effect of radiation therapy of I uptake in overexpressed PC3 cells.

关键词： androgen-independent prostate cancer     normal epithelial cell-specific 1/kallikrein 10     sodium/iodide symporter     radiation therapy     proliferation    

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Adenovirus-mediated tissue inhibitor of metalloproteinase-3 gene transfection inhibits rabbit intervertebral

Xudong YU MM, Zengwu SHAO MD, Liming XIONG MD, Weiwei XU MM, Hezhong WANG MM, Huifa XU MM,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 415-420 doi: 10.1007/s11684-009-0072-z

摘要： The aim of this study was to investigate the inhibitory effects of recombinant adenovirus vector carrying tissue inhibitor of metalloproteinase-3 (RAdTIMP-3) against degeneration of rabbit intervertebral disc. Thirty Japanese white rabbits of 4 months old were randomly divided into 5 groups. Mild or moderate rabbit lumbar disc degeneration model was constructed with the controllable axial loading device by imposing 98N pressure at the discs for 2 weeks. Various doses of virus were injected into the degenerated discs as follows: 20μL of normal saline in group 1; 20μL of RAd66 (an empty adenovirus vector, 1.0×10OPU/mL) in group 2; and 20, 10, and 5μL of RAdTIMP-3 (1.0×10OPU/mL) in groups 3, 4, and 5, respectively. Two weeks after the injection, the discs were collected for investigations, including assessment of degeneration degrees according to the Thompson’s grading system, reverse-transcription polymerase chain reaction (RT-PCR) assay for TIMP-3 gene, Safranin O-Fast green staining, and immunohistochemical staining for TIMP-3 and type II collagen. According to Thompson’s criteria, the degeneration of groups 3, 4, and 5, especially group 3, was alleviated as compared with groups 1 and 2. RT-PCR revealed that the expression of TIMP-3 in groups 3, 4, and 5, especially in group 3, was significantly enhanced as compared with group 1 (<0.01). Both Safranin O-Fast green staining and type II collagen staining demonstrated better reserved integrity of disc matrix in groups 3, 4, and 5 than in groups 1 and 2. TIMP-3 staining exhibited an obvious increase of positive-staining rate in groups 3, 4, and 5 as compared with group 1. The positive-staining rate in group 3 (79.42%±1.35%) was about 3times that of group 1 (25.47%±5.46%, <0.01). RAdTIMP-3 can effectively protect the matrix of rabbit intervertebral disc against overloading-induced degeneration in a dose-dependent manner, resulting in the alleviation of disc degeneration.

关键词： tissue inhibitor of metalloproteinase-3     intervertebral disc     rabbit     gene therapy    

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Genetic and clinical markers for predicting treatment responsiveness in rheumatoid arthritis

Xin Wu, Xiaobao Sheng, Rong Sheng, Hongjuan Lu, Huji Xu

《医学前沿（英文）》 2019年 第13卷 第4期   页码 411-419 doi: 10.1007/s11684-018-0659-3

摘要： Although many drugs and therapeutic strategies have been developed for rheumatoid arthritis (RA) treatment, numerous patients with RA fail to respond to currently available agents. In this review, we provide an overview of the complexity of this autoimmune disease by showing the rapidly increasing number of genes associated with RA. We then systematically review various factors that have a predictive value (predictors) for the response to different drugs in RA treatment, especially recent advances. These predictors include but are certainly not limited to genetic variations, clinical factors, and demographic factors. However, no clinical application is currently available. This review also describes the challenges in treating patients with RA and the need for personalized medicine. At the end of this review, we discuss possible strategies to enhance the prediction of drug responsiveness in patients with RA.

关键词： rheumatoid arthritis     gene     clinical markers     therapy    

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Development of a magnetite-gene complex for gene transfection

Jian XIN BM, Ze-Feng XIA MD, Kai-Xiong TAO MD, Kai-Lin CAI PhD, Gao-Xiong HAN MD, Xiao-Ming SHUAI MD, Ji-Liang WANG MD, Han-Song DU MD, Guo-Bin WANG PhD, Yan LUO MM,

《医学前沿（英文）》 2010年 第4卷 第2期   页码 241-246 doi: 10.1007/s11684-010-0032-7

摘要： The key to successful gene therapy is to find a suitable method and carrier for transfection to allow a gene to be transferred into a cell and integrated into the target gene. The aim of this study was to determine whether biomagnetic material could be combined with the nucleic acid for gene transfection. Dextran-coated iron oxide nanoparticles (DCIONPs) were prepared and mixed with the plasmid pGenesil-1 containing the test gene, which expresses enhanced green fluorescent protein (eGFP). PGenesil-1 empty vector was used as a control. The binding ability was assessed by electrophoresis of the DNA on agarose gels and quantification using BANDSCAN software. Using different gene carriers, Lipofectamine 2000, Sofast, and DCIONPs, the large intestine cancer (Lovo) cell line was transfected with or without a magnetic field. The expression of eGFP was observed by fluorescence microscopy, and the transfection efficiency was compared. The results showed there was a rapid increase in combining rate when the quality ratio of DCIONPs and pGenesil-1 ascended from 1∶1 to 5∶1. However, the combining rate increased less rapidly as the quality ratio continued ascending. The expression of eGFP showed that the early transfection rate could be improved by applying a magnetic field. In conclusion, the DCIONPs we synthesized are able to carry plasmid DNA and enhance the early transfection efficiency when using a magnetic field.

关键词： nanoparticle     magnetite     gene therapy     magnetofection    

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Molecular classification of non-small-cell lung cancer: diagnosis, individualized treatment, and prognosis

null

《医学前沿（英文）》 2013年 第7卷 第2期   页码 157-171 doi: 10.1007/s11684-013-0272-4

摘要：

Non-small-cell lung cancer (NSCLC) is the most common cause of premature death among the malignant diseases worldwide. The current staging criteria do not fully capture the complexity of this disease. Molecular biology techniques, particularly gene expression microarrays, proteomics, and next-generation sequencing, have recently been developed to facilitate effectively its molecular classification. The underlying etiology, pathogenesis, therapeutics, and prognosis of NSCLC based on an improved molecular classification scheme may promote individualized treatment and improve clinical outcomes. This review focuses on the molecular classification of NSCLC based on gene expression microarray technology reported during the past decade, as well as their applications for improving the diagnosis, staging and treatment of NSCLC, including the discovery of prognostic markers or potential therapeutic targets. We highlight some of the recent studies that may refine the identification of NSCLC subtypes using novel techniques such as epigenetics, proteomics, or deep sequencing.

关键词： non-small-cell lung cancer     molecular typing     individualized medicine     molecular-targeted therapy     gene expression profiling    

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Long-term correction of hemorrhagic diathesis in hemophilia A mice by an AAV-delivered hybrid FVIII composed of the human heavy chain and the rat light chain

《医学前沿（英文）》 2022年 第16卷 第4期   页码 584-595 doi: 10.1007/s11684-021-0844-7

摘要： Conventional therapies for hemophilia A (HA) are prophylactic or on-demand intravenous FVIII infusions. However, they are expensive and inconvenient to perform. Thus, better strategies for HA treatment must be developed. In this study, a recombinant FVIII cDNA encoding a human/rat hybrid FVIII with an enhanced procoagulant potential for adeno-associated virus (AAV)-delivered gene therapy was developed. Plasmids containing human FVIII heavy chain (hHC), human light chain (hLC), and rat light chain (rLC) were transfected into cells and hydrodynamically injected into HA mice. Purified AAV viruses were intravenously injected into HA mice at two doses. Results showed that the hHC+ rLC protein had a higher activity than the hHC+ hLC protein at comparable expression levels. The specific activity of hHC+ rLC was about 4- to 8-fold higher than that of their counterparts. Hydrodynamic injection experiments obtained consistent results. Notably, the HA mice undergoing the AAV-delivered hHC+ rLC treatment exhibited a visibly higher activity than those treated with hHC+ hLC, and the therapeutic effects lasted for up to 40 weeks. In conclusion, the application of the hybrid FVIII (hHC+ rLC) via an AAV-delivered gene therapy substantially improved the hemorrhagic diathesis of the HA mice. These data might be of help to the development of optimized FVIII expression cassette for HA gene therapy.

关键词： hemophilia A     adeno-associated virus (AAV)     human/rat hybrid factor VIII     gene therapy     dual chain strategy    

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Cotransfecting norepinephrine transporter and vesicular monoamine transporter 2 genes for increased retention of metaiodobenzylguanidine labeled with iodine 131 in malignant hepatocarcinoma cells

null

《医学前沿（英文）》 2017年 第11卷 第1期   页码 120-128 doi: 10.1007/s11684-017-0501-3

摘要：

Norepinephrine transporter (NET) transfection leads to significant uptake of iodine-131-labeled metaiodobenzylguanidine (131I-MIBG) in non-neuroendocrine tumors. However, the use of 131I-MIBG is limited by its short retention time in target cells. To prolong the retention of 131I-MIBG in target cells, we infected hepatocarcinoma (HepG2) cells with Lentivirus-encoding human NET and vesicular monoamine transporter 2 (VMAT2) genes to obtain NET-expressing, NET-VMAT2-coexpressing, and negative-control cell lines. We evaluated the uptake and efflux of 131I-MIBG both in vitro and in vivo in mice bearing transfected tumors. NET-expressing and NET-VMAT2-coexpressing cells respectively showed 2.24 and 2.22 times higher 131I-MIBG uptake than controls. Two hours after removal of 131I-MIBG-containing medium, 25.4% efflux was observed in NET-VMAT2-coexpressing cells and 38.6% in NET-expressing cells. In vivo experiments were performed in nude mice bearing transfected tumors; results revealed that NET-VMAT2-coexpressing tumors had longer 131I-MIBG retention time than NET-expressing tumors. Meanwhile, NET-VMAT2-coexpressing and NET-expressing tumors displayed 0.54% and 0.19%, respectively, of the injected dose per gram of tissue 24 h after 131I-MIBG administration. Cotransfection of HepG2 cells with NET and VMAT2resulted in increased 131I-MIBG uptake and retention. However, the degree of increase was insufficient to be therapeutically effective in target cells.

关键词： norepinephrine transporter     vesicular monoamine transporter 2     -MIBG     gene therapy     lentivirus vector    

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标题 作者 时间 类型 操作

Stem cell gene therapy: the risks of insertional mutagenesis and approaches to minimize genotoxicity

Chuanfeng Wu, Cynthia E. Dunbar

期刊论文

Optimized human factor IX expression cassettes for hepatic-directed gene therapy of hemophilia B

null

期刊论文

Gene therapy for hemophilia B mice with scAAV8-LP1-hFIX

null

期刊论文

Molecular engineering of dendrimer nanovectors for siRNA delivery and gene silencing

Yu Cao, Xiaoxuan Liu, Ling Peng

期刊论文

Investigation of gene therapy of denovirus in immune suppression

XIA Xi, WANG Beibei, CAO Li, CHEN Gang, WU Peng, LU Yunping, ZHOU Jianfeng, MA Ding

期刊论文

Construction of lentiviral vector carrying Rab9 gene and its expression in mouse brain

Youguo HAO, Min ZHANG, Jinzhi XU, Bitao BU, Jiajun WEI

期刊论文

Adenovirus-mediated antisense ERK2 gene therapy ameliorates chronic allograft nephropathy in a rat model

Zhao DING, Zhishui CHEN, Xilin CHEN, Ming CAI, Hui GUO, Nianqiao GONG

期刊论文

Antitumor immunity of human SART3 gene vaccine against mouse tumor

HE Yu, YANG Shuhua, LIU Yong, LI Tao

期刊论文

NES1/KLK10 and hNIS gene therapy enhanced iodine-131 internal radiation in PC3 proliferation

Jiajia Hu, Wenbin Shen, Qian Qu, Xiaochun Fei, Ying Miao, Xinyun Huang, Jiajun Liu, Yingli Wu, Biao Li

期刊论文

Adenovirus-mediated tissue inhibitor of metalloproteinase-3 gene transfection inhibits rabbit intervertebral

Xudong YU MM, Zengwu SHAO MD, Liming XIONG MD, Weiwei XU MM, Hezhong WANG MM, Huifa XU MM,

期刊论文

Genetic and clinical markers for predicting treatment responsiveness in rheumatoid arthritis

Xin Wu, Xiaobao Sheng, Rong Sheng, Hongjuan Lu, Huji Xu

期刊论文

Development of a magnetite-gene complex for gene transfection

Jian XIN BM, Ze-Feng XIA MD, Kai-Xiong TAO MD, Kai-Lin CAI PhD, Gao-Xiong HAN MD, Xiao-Ming SHUAI MD, Ji-Liang WANG MD, Han-Song DU MD, Guo-Bin WANG PhD, Yan LUO MM,

期刊论文

Molecular classification of non-small-cell lung cancer: diagnosis, individualized treatment, and prognosis

null

期刊论文

Long-term correction of hemorrhagic diathesis in hemophilia A mice by an AAV-delivered hybrid FVIII composed of the human heavy chain and the rat light chain

期刊论文

Cotransfecting norepinephrine transporter and vesicular monoamine transporter 2 genes for increased retention of metaiodobenzylguanidine labeled with iodine 131 in malignant hepatocarcinoma cells

null

期刊论文