Autophagy is a "self-degradative" process and is involved in the maintenance of cellular homeostasis and the control of cellular components by facilitating the clearance or turnover of long-lived or misfolde...Autophagy is a "self-degradative" process and is involved in the maintenance of cellular homeostasis and the control of cellular components by facilitating the clearance or turnover of long-lived or misfolded proteins, protein aggregates, and damaged organelles. Autophagy plays a dual role in cancer, including in tumor progression and tumor promotion, suggesting that autophagy acts as a double-edged sword in cancer cells. Liver cancer is one of the greatest leading causes of cancer death worldwide due to its high recurrence rate and poor prognosis. Especially in China, liver cancer has become one of the most common cancers due to the high infection rate of hepatitis virus. In primary liver cancer, hepatocellular carcinoma (HCC) is the most common type. Considering the perniciousness and complexity of HCC, it is essential to elucidate the function of autophagy in HCC. In this review, we summarize the physiological function of autophagy in cancer, analyze the role of autophagy in tumorigenesis and metastasis, discuss the therapeutic strategies targeting autophagy and the mechanisms of drug-resistance in HCC, and provide potential methods to circumvent resistance and combined anticancer strategies for HCC patients.展开更多
Cancer cells possess metabolic properties that are different from those of benign cells.p21,encoded by CDKN1A gene,also named p21Cip1/WAF1,was first identified as a cyclin-dependent kinase regulator that suppresses ce...Cancer cells possess metabolic properties that are different from those of benign cells.p21,encoded by CDKN1A gene,also named p21Cip1/WAF1,was first identified as a cyclin-dependent kinase regulator that suppresses cell cycle G1/S phase and retinoblastoma protein phosphorylation.CDKN1A(p21)acts as the downstream target gene of TP53(p53),and its expression is induced by wild-type p53 and it is not associated with mutant p53.p21 has been characterized as a vital regulator that involves multiple cell functions,including G1/S cell cycle progression,cell growth,DNA damage,and cell stemness.In 1994,p21 was found as a tumor suppressor in brain,lung and colon cancer by targeting p53 and was associated with tumorigenesis and metastasis.Notably,p21 plays a significant role in tumor development through p53-dependent and p53-independent pathways.In addition,expression of p21 is closely related to the resting state or terminal differentiation of cells.p21 is also associated with cancer stem cells and acts as a biomarker for such cells.In cancer therapy,given the importance of p21 in regulating the G1/S and G2 check points,it is not surprising that p21 is implicated in response to many cancer treatments and p21 promotes the effect of oncolytic virotherapy.展开更多
Receptor tyrosine kinase-like orphan receptor 1(ROR1)is a member of the type I receptor tyrosine kinase family.ROR1 is pivotal in embryonic development and cancer,and serves as a biomarker and therapeutic target.It ha...Receptor tyrosine kinase-like orphan receptor 1(ROR1)is a member of the type I receptor tyrosine kinase family.ROR1 is pivotal in embryonic development and cancer,and serves as a biomarker and therapeutic target.It has soluble and membrane-bound subtypes,with the latter highly expressed in tumors.ROR1 is conserved throughout evolution and may play a role in the development of gastrointestinal cancer through multiple signaling pathways and molecular mechanisms.Studies suggest that overexpression of ROR1 may increase tumor invasiveness and metastasis.Additionally,ROR1 may regulate the cell cycle,stem cell characteristics,and interact with other signaling pathways to affect cancer progression.This review explores the structure,expression and role of ROR1 in the development of gastrointestinal cancers.It discusses current antitumor strategies,outlining challenges and prospects for treatment.展开更多
AIM: To construct a tumor-selective replication-competent adenovirus (RCAd), SG300, using a modified promoter of human telomerase reverse transcriptase (hTERT). METHODS: The antitumor efficacy of SG300 in hepatocellul...AIM: To construct a tumor-selective replication-competent adenovirus (RCAd), SG300, using a modified promoter of human telomerase reverse transcriptase (hTERT). METHODS: The antitumor efficacy of SG300 in hepatocellular carcinoma was assessed in vitro and in vivo. In vitro cell viability by MTT assay was used to assess the tumor-selective oncolysis and safety features of SG300, and in vivo antitumor activity of SG300 was assessed in established hepatocellular carcinoma models in nude mice. RESULTS: SG300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI), but could not affect growth of normal cells even at a high MOI. Both in Hep3B and SMMC-7721 xenograft models of hepatocellular carcinoma, SG300 had an obvious antitumor effect, resulting in a decrease in tumor volume. Its selective oncolysis to tumor cells and safety to normal cells was also superior to that of ONYX-015. Pathological examination of tumor specimens showed that SG300 replicated selectively in cancer cells and resulted in apoptosis and necrosis of cancer cells. CONCLUSION: hTERT promoter-regulated replicativeadenovirus SG300 has a better cancer-selective replication-competent ability, and can specifically kill a wide range of cancer cells with positive telomerase activity, and thus has better potential for targeting therapy of hepatocellular carcinoma.展开更多
Human hepatocellular carcinoma(HCC)heavily endangers human heath worldwide.HCC is one of most frequent cancers in China because patients with liver disease,such as chronic hepatitis,have the highest cancer susceptibil...Human hepatocellular carcinoma(HCC)heavily endangers human heath worldwide.HCC is one of most frequent cancers in China because patients with liver disease,such as chronic hepatitis,have the highest cancer susceptibility.Traditional therapeutic approaches have limited efficacy in advanced liver cancer,and novel strategies are urgently needed to improve the limited treatment options for HCC.This review summarizes the basic knowledge,current advances,and future challenges and prospects of adeno-associated virus(AAV)and adenoviruses as vectors for gene therapy of HCC.This paper also reviews the clinical trials of gene therapy using adenovirus vectors,immunotherapy,toxicity and immunological barriers for AAV and adenoviruses,and proposes several alternative strategies to overcome the therapeutic barriers to using AAV and adenoviruses as vectors.展开更多
Due to concerns regarding the overlapping figures in this review that are identical to those contained in a reviewarticle that we have co-authored and published earlier,we retract the above paper we published in Cell ...Due to concerns regarding the overlapping figures in this review that are identical to those contained in a reviewarticle that we have co-authored and published earlier,we retract the above paper we published in Cell Research.Weapologize for any confusion that may be caused by this matter,although we stand by the scientific contents containedin the Cell Research paper.展开更多
Gastrointestinal cancer has been one of the five most commonly diagnosed and leading causes of cancer mortality over the past few decades. Great progress in traditional therapies has been made, which prolonged surviva...Gastrointestinal cancer has been one of the five most commonly diagnosed and leading causes of cancer mortality over the past few decades. Great progress in traditional therapies has been made, which prolonged survival in patients with early cancer, yet tumor relapse and drug resistance still occurred, which is explained by the cancer stem cell(CSC) theory. Oncolytic virotherapy has attracted increasing interest in cancer because of its ability to infect and lyse CSCs. This paper reviews the basic knowledge, CSC markers and therapeutics of gastrointestinal cancer(liver, gastric, colon and pancreatic cancer), as well as research advances and possible molecular mechanisms of various oncolytic viruses against gastrointestinal CSCs. This paper also summarizes the existing obstacles to oncolytic virotherapy and proposes several alternative suggestions to overcome the therapeutic limitations.展开更多
In this paper, silk sericin was employed to regulate the mineralization of calcium carbonate (CaC03). CaCO3 composite particles were prepared by the precipita- tion reaction of sodium carbonate with calcium chloride...In this paper, silk sericin was employed to regulate the mineralization of calcium carbonate (CaC03). CaCO3 composite particles were prepared by the precipita- tion reaction of sodium carbonate with calcium chloride solution in the presence of silk sericin. The as-prepared samples were collected at different reaction time to study the crystallization process of CaCO3 by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and X-ray diffraction (XRD). The results showed that silk sericin significantly affected the morphology and crystallographic polymorph of CaCO3. With increasing the reaction time, the crystal phase of CaCO3 transferred from calcite dominated to vaterite dominated mixtures, while the morphology of CaCO3 changed from disk-like calcite crystal to spherical vaterite crystal. These studies showed the potential of silk sericin used as a template molecule to control the growth of inorganic crystal.展开更多
Targeting is critical for successful tumor gene therapy.The adeno-associated virus(AAV) has aroused wide concern due to its excellent advantages over other viral vectors in gene therapy.AAV has a broad infection spect...Targeting is critical for successful tumor gene therapy.The adeno-associated virus(AAV) has aroused wide concern due to its excellent advantages over other viral vectors in gene therapy.AAV has a broad infection spectrum,which also results in poor specificity towards tissues or cells and low transduction efficiency.Therefore,it is imperative to improve target and transduction efficiency in AAV-mediated gene therapy.Up to now,researchers have developed many strategies to modify AAV capsids for improving targeting or retargeting only desired cells.These strategies include not only traditional chemical modification,phage display technology,modification of AAV capsid genome,chimeric vectors and so on,but also many novel strategies involved in marker rescue strategy,direct evolution of capsid proteins,direct display random peptides on AAV capsid,AAVP(AAV-Phage),and etc.This review will summarize the advances of researches on the capsid modification of AAV to target malignant cells.展开更多
Dear Editor, PD-L1, also known as CD274, plays a vital role in tumor cell related immune escape. It can be expressed on the cell surface of many solid tumors (Brahmer et al., 2012) and inhibits T cell proliferation ...Dear Editor, PD-L1, also known as CD274, plays a vital role in tumor cell related immune escape. It can be expressed on the cell surface of many solid tumors (Brahmer et al., 2012) and inhibits T cell proliferation and cytokine production by bind- ing to the Tcell surface receptor programmed death 1 (PD-1) or B7-1 (McClanahan et al., 2015). In 2013, targeting PD-1/ PD-L1 signaling for cancer immunotherapy was selected as the No.1 scientific breakthrough of the year by the editors of Science. Interferons (IFNs) are a group of pleiotropic cytokines, demonstrated anti-viral, anti-tumor, and immune regulatory functions (York et al., 2015). Type I interferon binds a heterodimeric receptor composed of IFNAR1 and IFNAR2. This activates a canonical JAK/STAT signaling pathway that ultimately induces a set of interferon-stimulated genes to exert its biological activity (Ejlerskov et al., 2015). Recently, PD-L1 was reported to be downstream of IFN signaling in human oral squamous carcinoma, melanoma, and human acute myeloid leukemia blast cells (Chen et al., 2012; Furuta et al., 2014; Kronig et al., 2014).展开更多
In this study, silk scaffolds with appropriate porous structures were prepared by adjusting solution concentrations and providing treatment with methanol solutions in the way of freeze drying. The effects of the prepa...In this study, silk scaffolds with appropriate porous structures were prepared by adjusting solution concentrations and providing treatment with methanol solutions in the way of freeze drying. The effects of the preparation conditions on the microstructures and properties of the scaffolds were discussed. Fibroin solutions with different concentrations of 4, 6, 8, 10 wt% were used respectively to prepare the scaffolds. The effects of the addition of 20 vol% methanol before or after freeze drying to the 4 wt% fibroin solution were investigated. As demonstrated by Scanning Electron Microscope (SEM), the fib-roin scaffolds prepared without methanol had porous microstructures composed of thin sheets, and the sizes of the pores decreased with the increase of the fibroin solution concentrations, while the scaffolds prepared in the presence of methanol showed porous microstructures formed by fine-particle aggregates. The porosities and mechanical properties of the prepared fibroin scaffolds under different conditions were tested. The crystalline structures and conformations of the fibroin scaffolds were detected by Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD).展开更多
Adeno-associated virus (AAV) has rapidly become a promising gene delivery vector for its excellent advantages of low pathogenicity and long-term gene expression over other viral vectors for human gene therapy. However...Adeno-associated virus (AAV) has rapidly become a promising gene delivery vector for its excellent advantages of low pathogenicity and long-term gene expression over other viral vectors for human gene therapy. However, the disadvantage of AAV for clinical gene therapy is the broad host range and the lack of tissue or cell specificity, which makes AAVs relatively inefficient gene delivery to target cells and short of safety. Therefore, it is required to improve the targeting capability of recombinant adeno-associated virus (rAAV) for successful gene therapy. At present, the successful identification of vari- ous-serotype AAVs and the improvement of rAAV production technology make it feasible to explore new applications of rAAV vector in clinical gene therapy trials. Moreover, the current development in targeting strategy has brought a bright prospect to rAAV vectors. Many studies have demonstrated that targeting gene therapy based on rAAV vectors could be achieved through transcription targeted, con-jugate targeted, receptor targeted, gene recombinant targeted strategies, etc. This report gives a com- prehensive review of the recent developments of targeting strategies for rAAV vectors.展开更多
Adeno-associated virus(AAV)is a promising viral vector and meets most requirements of being a safe biological agent.However,the commercialization of AAV has been hampered due to the limitation of large-scale productio...Adeno-associated virus(AAV)is a promising viral vector and meets most requirements of being a safe biological agent.However,the commercialization of AAV has been hampered due to the limitation of large-scale production,and only a small number of clinical trials have been launched.In recent years,progresses in scalable manufacturing of AAV have dramatically improved AAVbased clinical researches,and have assisted the development of investigational drug products.An AAV1-based investigational product,Glybera,has been formally approved by European Commission for the treatment of lipoprotein lipase deficiency(LPLD).Glybera was the first gene therapy product in the western world,and the production process involves a scalable baculovirus-insect cell system.However,many problems still need to be solved to improve the productivity and quality of AAV.The present review gives critical insights into current state-of-the-art scalable producing methodologies of AAV,such as baculovirus-insect cell system,HSV complementation system,and Ad complementation system,along with a discussion on the problems,solutions,and developmental trends.Novel AAV-producing platforms in Saccharomyces cerevisiae and vaccinia virus complementation system will also be discussed.展开更多
基金Supported by Natural Science Foundation of China,No.81803069Natural Science Foundation of Zhejiang Province of China,No.LY18C070002 and No.LY16H160056521 Talent Project of Zhejiang Sci-Tech University
文摘Autophagy is a "self-degradative" process and is involved in the maintenance of cellular homeostasis and the control of cellular components by facilitating the clearance or turnover of long-lived or misfolded proteins, protein aggregates, and damaged organelles. Autophagy plays a dual role in cancer, including in tumor progression and tumor promotion, suggesting that autophagy acts as a double-edged sword in cancer cells. Liver cancer is one of the greatest leading causes of cancer death worldwide due to its high recurrence rate and poor prognosis. Especially in China, liver cancer has become one of the most common cancers due to the high infection rate of hepatitis virus. In primary liver cancer, hepatocellular carcinoma (HCC) is the most common type. Considering the perniciousness and complexity of HCC, it is essential to elucidate the function of autophagy in HCC. In this review, we summarize the physiological function of autophagy in cancer, analyze the role of autophagy in tumorigenesis and metastasis, discuss the therapeutic strategies targeting autophagy and the mechanisms of drug-resistance in HCC, and provide potential methods to circumvent resistance and combined anticancer strategies for HCC patients.
基金Supported by the Natural Science Foundation of Zhejiang Province of China,No. LY18C070002 and No.LY16H160056National Natural Science Foundation of China,No.81803069+1 种基金the 521 Talent Project of Zhejiang Sci-Tech UniversityScience Foundation of Zhejiang Sci Tech University,No. 18042291Y。
文摘Cancer cells possess metabolic properties that are different from those of benign cells.p21,encoded by CDKN1A gene,also named p21Cip1/WAF1,was first identified as a cyclin-dependent kinase regulator that suppresses cell cycle G1/S phase and retinoblastoma protein phosphorylation.CDKN1A(p21)acts as the downstream target gene of TP53(p53),and its expression is induced by wild-type p53 and it is not associated with mutant p53.p21 has been characterized as a vital regulator that involves multiple cell functions,including G1/S cell cycle progression,cell growth,DNA damage,and cell stemness.In 1994,p21 was found as a tumor suppressor in brain,lung and colon cancer by targeting p53 and was associated with tumorigenesis and metastasis.Notably,p21 plays a significant role in tumor development through p53-dependent and p53-independent pathways.In addition,expression of p21 is closely related to the resting state or terminal differentiation of cells.p21 is also associated with cancer stem cells and acts as a biomarker for such cells.In cancer therapy,given the importance of p21 in regulating the G1/S and G2 check points,it is not surprising that p21 is implicated in response to many cancer treatments and p21 promotes the effect of oncolytic virotherapy.
基金Supported by the Hangzhou Medical Health Science and Technology Project,No.B20220173the Public Welfare Technology Project of Zhejiang Province,No.LGF21H160033Zhejiang Medical Technology Plan Project,No.2021KY047.
文摘Receptor tyrosine kinase-like orphan receptor 1(ROR1)is a member of the type I receptor tyrosine kinase family.ROR1 is pivotal in embryonic development and cancer,and serves as a biomarker and therapeutic target.It has soluble and membrane-bound subtypes,with the latter highly expressed in tumors.ROR1 is conserved throughout evolution and may play a role in the development of gastrointestinal cancer through multiple signaling pathways and molecular mechanisms.Studies suggest that overexpression of ROR1 may increase tumor invasiveness and metastasis.Additionally,ROR1 may regulate the cell cycle,stem cell characteristics,and interact with other signaling pathways to affect cancer progression.This review explores the structure,expression and role of ROR1 in the development of gastrointestinal cancers.It discusses current antitumor strategies,outlining challenges and prospects for treatment.
基金Supported by the Natural Science Foundation of China, No. 30572149 the National 863 High Technology R&D Project of China, No. 2003AA216030
文摘AIM: To construct a tumor-selective replication-competent adenovirus (RCAd), SG300, using a modified promoter of human telomerase reverse transcriptase (hTERT). METHODS: The antitumor efficacy of SG300 in hepatocellular carcinoma was assessed in vitro and in vivo. In vitro cell viability by MTT assay was used to assess the tumor-selective oncolysis and safety features of SG300, and in vivo antitumor activity of SG300 was assessed in established hepatocellular carcinoma models in nude mice. RESULTS: SG300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI), but could not affect growth of normal cells even at a high MOI. Both in Hep3B and SMMC-7721 xenograft models of hepatocellular carcinoma, SG300 had an obvious antitumor effect, resulting in a decrease in tumor volume. Its selective oncolysis to tumor cells and safety to normal cells was also superior to that of ONYX-015. Pathological examination of tumor specimens showed that SG300 replicated selectively in cancer cells and resulted in apoptosis and necrosis of cancer cells. CONCLUSION: hTERT promoter-regulated replicativeadenovirus SG300 has a better cancer-selective replication-competent ability, and can specifically kill a wide range of cancer cells with positive telomerase activity, and thus has better potential for targeting therapy of hepatocellular carcinoma.
基金We thank Lanying Sun, Yang Xiao, Yuelei Chen, Hua Zhou and Cell Analysis Center (Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences) for professional technical assistance. This work was supported in part by grants from Hi-Tech Research Development Program of China (863 Program, No. 2007AA021006) the Key Project of the Chinese Academy of Sciences (No. KSCX2-YW- R-09)+1 种基金 the 973 Project (No. 2004CB518804) Grant 30623003 from National Nature Science Foundation of China and Grant 06DZ22032 from Science and Technology Commission of Shang- hai Municipality.
基金Supported by National Natural Science Foundation of China.No.81272687Zhejiang Provincial Public Welfare Technology Application Research Projects,No.2014C33275+1 种基金Zhejiang Provincial Natural Science Foundation of China,No.LZ13H160004the Grant for 521 Talent Project of Zhejiang Sci-Tech University,Hangzhou,China
文摘Human hepatocellular carcinoma(HCC)heavily endangers human heath worldwide.HCC is one of most frequent cancers in China because patients with liver disease,such as chronic hepatitis,have the highest cancer susceptibility.Traditional therapeutic approaches have limited efficacy in advanced liver cancer,and novel strategies are urgently needed to improve the limited treatment options for HCC.This review summarizes the basic knowledge,current advances,and future challenges and prospects of adeno-associated virus(AAV)and adenoviruses as vectors for gene therapy of HCC.This paper also reviews the clinical trials of gene therapy using adenovirus vectors,immunotherapy,toxicity and immunological barriers for AAV and adenoviruses,and proposes several alternative strategies to overcome the therapeutic barriers to using AAV and adenoviruses as vectors.
文摘Due to concerns regarding the overlapping figures in this review that are identical to those contained in a reviewarticle that we have co-authored and published earlier,we retract the above paper we published in Cell Research.Weapologize for any confusion that may be caused by this matter,although we stand by the scientific contents containedin the Cell Research paper.
基金Supported by the National Natural Science Foundation of China,No.81272687the Natural Science Foundation of Zhejiang Province of China,No.LZ13H160004 and No.LY16H160056the 521 Talent Project of Zhejiang Sci-Tech University
文摘Gastrointestinal cancer has been one of the five most commonly diagnosed and leading causes of cancer mortality over the past few decades. Great progress in traditional therapies has been made, which prolonged survival in patients with early cancer, yet tumor relapse and drug resistance still occurred, which is explained by the cancer stem cell(CSC) theory. Oncolytic virotherapy has attracted increasing interest in cancer because of its ability to infect and lyse CSCs. This paper reviews the basic knowledge, CSC markers and therapeutics of gastrointestinal cancer(liver, gastric, colon and pancreatic cancer), as well as research advances and possible molecular mechanisms of various oncolytic viruses against gastrointestinal CSCs. This paper also summarizes the existing obstacles to oncolytic virotherapy and proposes several alternative suggestions to overcome the therapeutic limitations.
文摘In this paper, silk sericin was employed to regulate the mineralization of calcium carbonate (CaC03). CaCO3 composite particles were prepared by the precipita- tion reaction of sodium carbonate with calcium chloride solution in the presence of silk sericin. The as-prepared samples were collected at different reaction time to study the crystallization process of CaCO3 by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and X-ray diffraction (XRD). The results showed that silk sericin significantly affected the morphology and crystallographic polymorph of CaCO3. With increasing the reaction time, the crystal phase of CaCO3 transferred from calcite dominated to vaterite dominated mixtures, while the morphology of CaCO3 changed from disk-like calcite crystal to spherical vaterite crystal. These studies showed the potential of silk sericin used as a template molecule to control the growth of inorganic crystal.
基金Supported by National Natural Science Foundation of China (Grant No.30772477)Natural Science Foundation of Zhejiang Province (Grant No.Y206481)
文摘Targeting is critical for successful tumor gene therapy.The adeno-associated virus(AAV) has aroused wide concern due to its excellent advantages over other viral vectors in gene therapy.AAV has a broad infection spectrum,which also results in poor specificity towards tissues or cells and low transduction efficiency.Therefore,it is imperative to improve target and transduction efficiency in AAV-mediated gene therapy.Up to now,researchers have developed many strategies to modify AAV capsids for improving targeting or retargeting only desired cells.These strategies include not only traditional chemical modification,phage display technology,modification of AAV capsid genome,chimeric vectors and so on,but also many novel strategies involved in marker rescue strategy,direct evolution of capsid proteins,direct display random peptides on AAV capsid,AAVP(AAV-Phage),and etc.This review will summarize the advances of researches on the capsid modification of AAV to target malignant cells.
文摘Dear Editor, PD-L1, also known as CD274, plays a vital role in tumor cell related immune escape. It can be expressed on the cell surface of many solid tumors (Brahmer et al., 2012) and inhibits T cell proliferation and cytokine production by bind- ing to the Tcell surface receptor programmed death 1 (PD-1) or B7-1 (McClanahan et al., 2015). In 2013, targeting PD-1/ PD-L1 signaling for cancer immunotherapy was selected as the No.1 scientific breakthrough of the year by the editors of Science. Interferons (IFNs) are a group of pleiotropic cytokines, demonstrated anti-viral, anti-tumor, and immune regulatory functions (York et al., 2015). Type I interferon binds a heterodimeric receptor composed of IFNAR1 and IFNAR2. This activates a canonical JAK/STAT signaling pathway that ultimately induces a set of interferon-stimulated genes to exert its biological activity (Ejlerskov et al., 2015). Recently, PD-L1 was reported to be downstream of IFN signaling in human oral squamous carcinoma, melanoma, and human acute myeloid leukemia blast cells (Chen et al., 2012; Furuta et al., 2014; Kronig et al., 2014).
基金the National Natural Science Foundation of China (Grant No. 50402001)the Laboratory Fund of Tsinghua University
文摘In this study, silk scaffolds with appropriate porous structures were prepared by adjusting solution concentrations and providing treatment with methanol solutions in the way of freeze drying. The effects of the preparation conditions on the microstructures and properties of the scaffolds were discussed. Fibroin solutions with different concentrations of 4, 6, 8, 10 wt% were used respectively to prepare the scaffolds. The effects of the addition of 20 vol% methanol before or after freeze drying to the 4 wt% fibroin solution were investigated. As demonstrated by Scanning Electron Microscope (SEM), the fib-roin scaffolds prepared without methanol had porous microstructures composed of thin sheets, and the sizes of the pores decreased with the increase of the fibroin solution concentrations, while the scaffolds prepared in the presence of methanol showed porous microstructures formed by fine-particle aggregates. The porosities and mechanical properties of the prepared fibroin scaffolds under different conditions were tested. The crystalline structures and conformations of the fibroin scaffolds were detected by Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD).
基金Supported by the Natural Science Foundation of Zhejiang Province (Grant No. Y205282)
文摘Adeno-associated virus (AAV) has rapidly become a promising gene delivery vector for its excellent advantages of low pathogenicity and long-term gene expression over other viral vectors for human gene therapy. However, the disadvantage of AAV for clinical gene therapy is the broad host range and the lack of tissue or cell specificity, which makes AAVs relatively inefficient gene delivery to target cells and short of safety. Therefore, it is required to improve the targeting capability of recombinant adeno-associated virus (rAAV) for successful gene therapy. At present, the successful identification of vari- ous-serotype AAVs and the improvement of rAAV production technology make it feasible to explore new applications of rAAV vector in clinical gene therapy trials. Moreover, the current development in targeting strategy has brought a bright prospect to rAAV vectors. Many studies have demonstrated that targeting gene therapy based on rAAV vectors could be achieved through transcription targeted, con-jugate targeted, receptor targeted, gene recombinant targeted strategies, etc. This report gives a com- prehensive review of the recent developments of targeting strategies for rAAV vectors.
基金supported by the National Natural Science Foundation of China (81071850 and 81301307)
文摘Adeno-associated virus(AAV)is a promising viral vector and meets most requirements of being a safe biological agent.However,the commercialization of AAV has been hampered due to the limitation of large-scale production,and only a small number of clinical trials have been launched.In recent years,progresses in scalable manufacturing of AAV have dramatically improved AAVbased clinical researches,and have assisted the development of investigational drug products.An AAV1-based investigational product,Glybera,has been formally approved by European Commission for the treatment of lipoprotein lipase deficiency(LPLD).Glybera was the first gene therapy product in the western world,and the production process involves a scalable baculovirus-insect cell system.However,many problems still need to be solved to improve the productivity and quality of AAV.The present review gives critical insights into current state-of-the-art scalable producing methodologies of AAV,such as baculovirus-insect cell system,HSV complementation system,and Ad complementation system,along with a discussion on the problems,solutions,and developmental trends.Novel AAV-producing platforms in Saccharomyces cerevisiae and vaccinia virus complementation system will also be discussed.
基金This work was in part supported by the National Basic Research Program of China (Grant No. 2011CB606205) and the National Natural Science Foundation of China (Grant Nos. 51272236 and 510O2139).