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 identifica...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.展开更多
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 ...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.展开更多
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.
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.
