|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Gene therapy: light is finally in the tunnel显示文摘After two decades of ups and downs,gene therapy has recently achieved a milestone in treating patients with Leber’s congenital amaurosis(LCA).LCA is a group of inherited blinding diseases with retinal degeneration and severe vision loss in early infancy.Mutations in several genes,including RPE65,cause the disease.Using adenoassociated virus as a vector,three independent teams of investigators have recently shown that RPE65 can be delivered to retinal pigment epithelial cells of LCA patients by subretinal injections resulting in clinical benefits without side effects.However,considering the whole field of gene therapy,there are still major obstacles to clinical applications for other diseases.These obstacles include innate and immune barriers to vector delivery,toxicity of vectors and the lack of sustained therapeutic gene expression.Therefore,new strategies are needed to overcome these hurdles for achieving safe and effective gene therapy.In this article,we shall review the major advancements over the past two decades and,using lung gene therapy as an example,discuss the current obstacles and possible solutions to provide a roadmap for future gene therapy research. | Huibi Cao Robert S.Molday Jim Hu | 2011 | Protein & Cell2011，2，12： | 9 |
| 2 | Regulation of epithelium-specific Ets-like factors ESE-1 and ESE-3 in airway epithelial cells: potential roles in airway inflammation显示文摘航线发炎是许多呼吸障碍的特点,例如气喘和膀胱的纤维变性。在发炎触发的航线基因表示的变化在这些疾病的致病起一个关键作用。基因连接研究建议 ESE-2 和 ESE-3,编码上皮特定的 Ets-domain-containing 抄写因素,是候选人气喘危险性基因。我们这里报导 et 家庭抄写因素 ESE-1 的另一个成员的表示,以及 ESE-3,起来在支气管的上皮的房间线由煽动性的 cytokines interleukin-1beta (IL-1beta ) 和肿瘤坏死 factor-alpha (TNF-alpha ) 调整了。有 IL-1beta 和 TNF-alpha 的这些房间的处理为 ESE-1 和 ESE-3 导致了信使 rna 表示的戏剧的增加。我们证明导致的表示被抄写因素 NF-kappaB 的激活调停。我们描绘了 ESE-1 和 ESE-3 倡导者并且识别了为导致 cytokine 的表达式被要求的 NF-kappaB 有约束力的序列。另外,我们也表明那 ESE-1 在上面调整 ESE-3 表示, down 由 cytokines 调整它的自己的正式就职。最后,我们在 Elf3 显示出那(对人的 ESE-1 相应) 猛烈老鼠,煽动性的 cytokine interleukin-6 (IL-6 ) 的表示是调整的 down。我们的调查结果建议 ESE-1 和 ESE-3 在航线发炎起一个重要作用。 | Jing Wu Rongqi Duan Huibi Cao Deborah Field Catherine M Newnham David R Koehler Noe Zamel Melanie A Pritchard Paul Hertzog Martin Post A Keith Tanswell Jim Hu | 2008 | Cell Research2008，18，6： | 6 |
| 3 | Potential of Helper-Dependent Adenoviral Vectors in Modulating Airway Innate Immunity显示文摘Innate immune responses form the first line of defense against foreign insults and recently significant advances have been made in our understanding of the initiation of innate immune response along with its ability to modulate inflammation. In airway diseases such as asthma, COPD and cystic fibrosis, over reacting of the airway innate immune responses leads to cytokine imbalance and airway remodeling or damage. Helper-dependent adenoviral vectors have the potential to deliver genes to modulate airway innate immune responses and have many advantages over its predecessors. However, there still are a few limitations that need to be addressed prior to their use in clinical applications. | Rahul Kushwah Huibi Cao Jim Hu | 2007 | Cellular & Molecular Immunology2007，4，2： | 2 |
| 4 | Lung gene therapydHow to capture illumination from the light already present in the tunnel显示文摘Gene therapy has been considered as the most ideal medical intervention for genetic diseases because it is intended to target the cause of diseases instead of disease symptoms.Availability of techniques for identification of genetic mutations and for in vitro manipulation of genes makes it practical and attractive.After the initial hype in 1990s and later disappointments in clinical trials formore than a decade,light has finally come into the tunnel in recent years,especially in the field of eye gene therapy where it has taken big strides.Clinical trials in gene therapy for retinal degenerative diseases such as Leber’s congenital amaurosis(LCA)and choroideremia demonstrated clear therapeutic efficacies without apparent side effects.Although these successful examples are still rare and sporadic in the field,they provide the proof of concept for harnessing the power of gene therapy to treat genetic diseases and to modernize our medication.In addition,those success stories illuminate the path for the development of gene therapy treating other genetic diseases.Because of the differences in target organs and cells,distinct barriers to gene delivery exist in gene therapy for each genetic disease.It is not feasible for authors to review the current development in the entire field.Thus,in this article,we will focus onwhatwe can learn from the current success in gene therapy for retinal degenerative diseases to speed up the gene therapy development for lung diseases,such as cystic fibrosis. | Emily Xia Manjunatha Ankathatti Munegowda Huibi Cao Jim Hu | 2014 | Genes & Diseases2014，1，1： | 2 |
| 5 | Highly efficient retinal gene delivery with helper-dependent adenoviral vectors显示文摘There have been significant advancements in the field of retinal gene therapy in the past several years.In particular,therapeutic efficacy has been achieved in three separate human clinical trials conducted to assess the ability of adeno-associated viruses(AAV)to treat of a type of Leber’s congenital amaurosis caused by RPE65 mutations.However,despite the success of retinal gene therapy with AAV,challenges remain for delivering large therapeutic genes or genes requiring long DNA regulatory elements for controlling their expression.For example,Stargardt’s disease,a form of juvenile macular degeneration,is caused by defects in ABCA4,a gene that is too large to be packaged in AAV.Therefore,we investigated the ability of helper dependent adenovirus(HD-Ad)to deliver genes to the retina as it has a much larger transgene capacity.Using an EGFP reporter,our results showed that HD-Ad can transduce the entire retinal epithelium of a mouse using a dose of only 1105 infectious units and maintain transgene expression for at least 4 months.The results demonstrate that HD-Ad has the potential to be an effective vector for the gene therapy of the retina. | Simon Lam Huibi Cao Jing Wu Rongqi Duan Jim Hu | 2014 | Genes & Diseases2014，1，2： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员