Lactobacillus species are non-spore-forming, gram-positive bacteria and lactic acid producing bacteria (LAPB) that naturally inhabit the human and animal gastrointestinal and mouth organs. The aim of this review was t...Lactobacillus species are non-spore-forming, gram-positive bacteria and lactic acid producing bacteria (LAPB) that naturally inhabit the human and animal gastrointestinal and mouth organs. The aim of this review was to evaluate the new progress regarding the use of Lactobacillus species as live delivery vectors, prevention, and treatment of pathogenic and metabolic diseases. Lactobacillus strains of probiotics have been extensively studied and have confirmed that they can absolutely improve performance as live delivery vectors, a treatment option of various diseases such as: Hemorrhagic cecal coccidiosis in young poultry, hypertension, avian flu, obesity, diabetes, Derzsy’s disease or parvovirus infection, human immunodeficiency virus infections, irritable bowel syndrome, gastrointestinal disorders, Fungal infections, vaginal eubiosis, fish and shellfish species diseases. We give you an idea about that Lactobacillus species have been proficient in preventing and treating both disorders in animal models and some are used for clinical trials. We present the most current studies on the use of Lactobacillus strains that had an impact on an effective immune response to a specific antigen because a variety of antigens have been expressed. Therefore Lactobacillus strains can be considered as good candidates because of its potential for diseases treatment and vaccine development as heterologous protein secretion to date.展开更多
Complications of the liver are amongst the world’s worst diseases.Liver fibrosis is the first stage of liver problems,while cirrhosis is the last stage,which can lead to death.The creation of effective anti-fibrotic ...Complications of the liver are amongst the world’s worst diseases.Liver fibrosis is the first stage of liver problems,while cirrhosis is the last stage,which can lead to death.The creation of effective anti-fibrotic drug delivery methods appears critical due to the liver’s metabolic capacity for drugs and the presence of insurmountable physiological impediments in the way of targeting.Recent breakthroughs in anti-fibrotic agents have substantially assisted in fibrosis;nevertheless,the working mechanism of anti-fibrotic medications is not fully understood,and there is a need to design delivery systems that are well-understood and can aid in cirrhosis.Nanotechnology-based delivery systems are regarded to be effective but they have not been adequately researched for liver delivery.As a result,the capability of nanoparticles in hepatic delivery was explored.Another approach is targeted drug delivery,which can considerably improve efficacy if delivery systems are designed to target hepatic stellate cells(HSCs).We have addressed numerous delivery strategies that target HSCs,which can eventually aid in fibrosis.Recently genetics have proved to be useful,and methods for delivering genetic material to the target place have also been investigated where different techniques are depicted.To summarize,this review paper sheds light on themost recent breakthroughs in drug and gene-based nano and targeted delivery systems that have lately shown useful for the treatment of liver fibrosis and cirrhosis.展开更多
The emergence of the clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)genome-editing system has brought about a significant revolution in the realm of managing human d...The emergence of the clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)genome-editing system has brought about a significant revolution in the realm of managing human diseases,establishing animal models,and so on.To fully harness the potential of this potent gene-editing tool,ensuring efficient and secure delivery to the target site is paramount.Consequently,developing effective delivery methods for the CRISPR/Cas9 system has become a critical area of research.In this review,we present a comprehensive outline of delivery strategies and discuss their biomedical applications in the CRISPR/Cas9 system.We also provide an indepth analysis of physical,viral vector,and non-viral vector delivery strategies,including plasmid-,mRNA-and protein-based approach.In addition,we illustrate the biomedical applications of the CRISPR/Cas9 system.This review highlights the key factors affecting the delivery process and the current challenges facing the CRISPR/Cas9 system,while also delineating future directions and prospects that could inspire innovative delivery strategies.This review aims to provide new insights and ideas for advancing CRISPR/Cas9-based delivery strategies and to facilitate breakthroughs in biomedical research and therapeutic applications.展开更多
Upon the discovery of RNA interference(RNAi),canonical small interfering RNA(si RNA) has been recognized to trigger sequence-specific gene silencing. Despite the benefits of si RNAs as potential new drugs,there are ob...Upon the discovery of RNA interference(RNAi),canonical small interfering RNA(si RNA) has been recognized to trigger sequence-specific gene silencing. Despite the benefits of si RNAs as potential new drugs,there are obstacles still to be overcome,including off-target effects and immune stimulation. More recently,Dicer substrate si RNA(Dsi RNA) has been introduced as an alternative to si RNA. Similarly,it also is proving to be potent and target-specific,while rendering less immune stimulation. Dsi RNA is 25–30 nucleotides in length,and is further cleaved and processed by the Dicer enzyme. As with si RNA,it is crucial to design and develop a stable,safe,and efficient system for the delivery of Dsi RNA into the cytoplasm of targeted cells. Several polymeric nanoparticle systems have been well established to load Dsi RNA for in vitro and in vivo delivery,thereby overcoming a major hurdle in the therapeutic uses of Dsi RNA. The present review focuses on a comparison of si RNA and Dsi RNA on the basis of their design,mechanism,in vitro and in vivo delivery,and therapeutics.展开更多
A 23 amino acid, bifunctional integrin-targeted synthetic oligopeptide was evaluated for ex vivo gene delivery to rabbit bone marrow stromal cells （BMSCs）. Synthesis of the peptide （K）16GRGDSPC was performed on a ...A 23 amino acid, bifunctional integrin-targeted synthetic oligopeptide was evaluated for ex vivo gene delivery to rabbit bone marrow stromal cells （BMSCs）. Synthesis of the peptide （K）16GRGDSPC was performed on a solid-phase batch peptide synthesizer. BMSCs were transfected with plasmid DNA coding for luciferase by （K）j6GRGDSPC and the transfection efficiency was assayed. The influences of chloroquine and polyethyleneimine on the transfection efficiency were also examined. The target specificity of （K）16GRGDSPC to mediate exogenous gene into BMSCs was analyzed using cell attachment test and gene delivery inhibition test. The results showed that the transfection efficiency of the oligopeptide vector was lower than that of Lipofectamine. But in the presence of endosomal buffer chloroquine or endosomal disrupting agent polyethyleneimine, the transfection efficiency of the vector was greatly enhanced. In addition, RGD-containing peptides inhibited BMSCs＇ attachment to the 96-well plates pretreated with fibronectin or vitronecfin and significantly decreased the transfection efficiency of the oligopeptide vector. These studies demonstrated that oligopeptide （K）16GRGDSPC was an ideal novel targeted non-viral gene delivery vector, which was easy to be synthesized, high efficient and low cytotoxicity. The vector could effectively deliver exogenous gene into rat BMSCs.展开更多
Anti-cancer therapies over the few decades, faced with many challenges. And bacterial vaccine vectors have shown a potential to be replaced as the cutting-edge technology for such aspects. Bacterial vaccine vectors wi...Anti-cancer therapies over the few decades, faced with many challenges. And bacterial vaccine vectors have shown a potential to be replaced as the cutting-edge technology for such aspects. Bacterial vaccine vectors with a suitable DNA can be a potential option for cancer treatment as a carrier for tumoricidal agents or bacterially directed Enzyme Prodrug treatment. Throughout this study, it is planned to have a review of the use of bacteria as vehicles by different ways for cancer treatment, detailing the systems of function and achievements at preclinical and clinical levels.展开更多
Gene therapy offers important perspectives in current and future medicine but suffers from imperfect vectors for the delivery of the therapeutic gene. Most preclinical and clinical trials have been based on the use of...Gene therapy offers important perspectives in current and future medicine but suffers from imperfect vectors for the delivery of the therapeutic gene. Most preclinical and clinical trials have been based on the use of viral vectors, which have evident advantages but also some serious disadvantages. In the past decade the use of DNA transposon-based systems for gene delivery has emerged as a non-viral alternative. DNA transposon vector engineering remains largely in a preclinical phase but some interesting results have been obtained. This mini-review aims to provide the current state of the art on DNA transposon vectors used in a gene therapy perspective.展开更多
Currently,there is no cure for traumatic spinal co rd injury but one therapeutic approach showing promise is gene therapy.In this systematic review and meta-analysis,we aim to assess the efficacy of gene therapies in ...Currently,there is no cure for traumatic spinal co rd injury but one therapeutic approach showing promise is gene therapy.In this systematic review and meta-analysis,we aim to assess the efficacy of gene therapies in pre-clinical models of spinal cord injury and the risk of bias.In this metaanalysis,registe red at PROSPERO(Registration ID:CRD42020185008),we identified relevant controlled in vivo studies published in English by searching the PubMed,Web of Science,and Embase databases.No restrictions of the year of publication were applied and the last literature search was conducted on August 3,2020.We then conducted a random-effects meta-analysis using the restricted maximum likelihood estimator.A total of 71 studies met our inclusion crite ria and were included in the systematic review.Our results showed that overall,gene therapies were associated with improvements in locomotor score(standardized mean difference[SMD]:2.07,95%confidence interval[CI]:1.68-2.47,Tau^(2)=2.13,I^(2)=83.6%)and axonal regrowth(SMD:2.78,95%CI:1.92-3.65,Tau^(2)=4.13,I^(2)=85.5%).There was significant asymmetry in the funnel plots of both outcome measures indicating the presence of publication bias.We used a modified CAMARADES(Collaborative Approach to M eta-Analysis and Review of Animal Data in Experimental Studies)checklist to assess the risk of bias,finding that the median score was 4(IQR:3-5).In particula r,reports of allocation concealment and sample size calculations were lacking.In conclusion,gene therapies are showing promise as therapies for spinal co rd injury repair,but there is no consensus on which gene or genes should be targeted.展开更多
文摘Lactobacillus species are non-spore-forming, gram-positive bacteria and lactic acid producing bacteria (LAPB) that naturally inhabit the human and animal gastrointestinal and mouth organs. The aim of this review was to evaluate the new progress regarding the use of Lactobacillus species as live delivery vectors, prevention, and treatment of pathogenic and metabolic diseases. Lactobacillus strains of probiotics have been extensively studied and have confirmed that they can absolutely improve performance as live delivery vectors, a treatment option of various diseases such as: Hemorrhagic cecal coccidiosis in young poultry, hypertension, avian flu, obesity, diabetes, Derzsy’s disease or parvovirus infection, human immunodeficiency virus infections, irritable bowel syndrome, gastrointestinal disorders, Fungal infections, vaginal eubiosis, fish and shellfish species diseases. We give you an idea about that Lactobacillus species have been proficient in preventing and treating both disorders in animal models and some are used for clinical trials. We present the most current studies on the use of Lactobacillus strains that had an impact on an effective immune response to a specific antigen because a variety of antigens have been expressed. Therefore Lactobacillus strains can be considered as good candidates because of its potential for diseases treatment and vaccine development as heterologous protein secretion to date.
文摘Complications of the liver are amongst the world’s worst diseases.Liver fibrosis is the first stage of liver problems,while cirrhosis is the last stage,which can lead to death.The creation of effective anti-fibrotic drug delivery methods appears critical due to the liver’s metabolic capacity for drugs and the presence of insurmountable physiological impediments in the way of targeting.Recent breakthroughs in anti-fibrotic agents have substantially assisted in fibrosis;nevertheless,the working mechanism of anti-fibrotic medications is not fully understood,and there is a need to design delivery systems that are well-understood and can aid in cirrhosis.Nanotechnology-based delivery systems are regarded to be effective but they have not been adequately researched for liver delivery.As a result,the capability of nanoparticles in hepatic delivery was explored.Another approach is targeted drug delivery,which can considerably improve efficacy if delivery systems are designed to target hepatic stellate cells(HSCs).We have addressed numerous delivery strategies that target HSCs,which can eventually aid in fibrosis.Recently genetics have proved to be useful,and methods for delivering genetic material to the target place have also been investigated where different techniques are depicted.To summarize,this review paper sheds light on themost recent breakthroughs in drug and gene-based nano and targeted delivery systems that have lately shown useful for the treatment of liver fibrosis and cirrhosis.
基金supported by the National Natural Science Foundation of China[32271464]the Hunan Provincial Natural Science Foundation for Distinguished Young Scholars[2022JJ10086]+4 种基金the Innovation-Driven Project of Central South University[2020CX048]the Joint Fund of the Hunan Provincial Natural Science Foundation and the Hunan Medical Products Adminstration[2023JJ60501]the Natural Science Foundation of Changsha[kq2202131]the Postgraduate Innovation Project of Central South University[2021zzts0977,2022ZZTS0980]the Hunan Provincial Innovation Foundation for Postgraduate[CX20210340,CX20220372].
文摘The emergence of the clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)genome-editing system has brought about a significant revolution in the realm of managing human diseases,establishing animal models,and so on.To fully harness the potential of this potent gene-editing tool,ensuring efficient and secure delivery to the target site is paramount.Consequently,developing effective delivery methods for the CRISPR/Cas9 system has become a critical area of research.In this review,we present a comprehensive outline of delivery strategies and discuss their biomedical applications in the CRISPR/Cas9 system.We also provide an indepth analysis of physical,viral vector,and non-viral vector delivery strategies,including plasmid-,mRNA-and protein-based approach.In addition,we illustrate the biomedical applications of the CRISPR/Cas9 system.This review highlights the key factors affecting the delivery process and the current challenges facing the CRISPR/Cas9 system,while also delineating future directions and prospects that could inspire innovative delivery strategies.This review aims to provide new insights and ideas for advancing CRISPR/Cas9-based delivery strategies and to facilitate breakthroughs in biomedical research and therapeutic applications.
基金financial support received from Centre of Research and Instrumentation (CRIM), Universiti Kebangsaan Malaysia
文摘Upon the discovery of RNA interference(RNAi),canonical small interfering RNA(si RNA) has been recognized to trigger sequence-specific gene silencing. Despite the benefits of si RNAs as potential new drugs,there are obstacles still to be overcome,including off-target effects and immune stimulation. More recently,Dicer substrate si RNA(Dsi RNA) has been introduced as an alternative to si RNA. Similarly,it also is proving to be potent and target-specific,while rendering less immune stimulation. Dsi RNA is 25–30 nucleotides in length,and is further cleaved and processed by the Dicer enzyme. As with si RNA,it is crucial to design and develop a stable,safe,and efficient system for the delivery of Dsi RNA into the cytoplasm of targeted cells. Several polymeric nanoparticle systems have been well established to load Dsi RNA for in vitro and in vivo delivery,thereby overcoming a major hurdle in the therapeutic uses of Dsi RNA. The present review focuses on a comparison of si RNA and Dsi RNA on the basis of their design,mechanism,in vitro and in vivo delivery,and therapeutics.
基金This project was supported by grants from National Natural Sciences Foundation of China (No. 30200063, 30470483).
文摘A 23 amino acid, bifunctional integrin-targeted synthetic oligopeptide was evaluated for ex vivo gene delivery to rabbit bone marrow stromal cells （BMSCs）. Synthesis of the peptide （K）16GRGDSPC was performed on a solid-phase batch peptide synthesizer. BMSCs were transfected with plasmid DNA coding for luciferase by （K）j6GRGDSPC and the transfection efficiency was assayed. The influences of chloroquine and polyethyleneimine on the transfection efficiency were also examined. The target specificity of （K）16GRGDSPC to mediate exogenous gene into BMSCs was analyzed using cell attachment test and gene delivery inhibition test. The results showed that the transfection efficiency of the oligopeptide vector was lower than that of Lipofectamine. But in the presence of endosomal buffer chloroquine or endosomal disrupting agent polyethyleneimine, the transfection efficiency of the vector was greatly enhanced. In addition, RGD-containing peptides inhibited BMSCs＇ attachment to the 96-well plates pretreated with fibronectin or vitronecfin and significantly decreased the transfection efficiency of the oligopeptide vector. These studies demonstrated that oligopeptide （K）16GRGDSPC was an ideal novel targeted non-viral gene delivery vector, which was easy to be synthesized, high efficient and low cytotoxicity. The vector could effectively deliver exogenous gene into rat BMSCs.
文摘Anti-cancer therapies over the few decades, faced with many challenges. And bacterial vaccine vectors have shown a potential to be replaced as the cutting-edge technology for such aspects. Bacterial vaccine vectors with a suitable DNA can be a potential option for cancer treatment as a carrier for tumoricidal agents or bacterially directed Enzyme Prodrug treatment. Throughout this study, it is planned to have a review of the use of bacteria as vehicles by different ways for cancer treatment, detailing the systems of function and achievements at preclinical and clinical levels.
文摘Gene therapy offers important perspectives in current and future medicine but suffers from imperfect vectors for the delivery of the therapeutic gene. Most preclinical and clinical trials have been based on the use of viral vectors, which have evident advantages but also some serious disadvantages. In the past decade the use of DNA transposon-based systems for gene delivery has emerged as a non-viral alternative. DNA transposon vector engineering remains largely in a preclinical phase but some interesting results have been obtained. This mini-review aims to provide the current state of the art on DNA transposon vectors used in a gene therapy perspective.
基金supported by Scottish Rugby Union,Graham and Pam Dixon,Medical Research Scotland,University of Aberdeen HOTSTART Scholarship Programme(to WH)。
文摘Currently,there is no cure for traumatic spinal co rd injury but one therapeutic approach showing promise is gene therapy.In this systematic review and meta-analysis,we aim to assess the efficacy of gene therapies in pre-clinical models of spinal cord injury and the risk of bias.In this metaanalysis,registe red at PROSPERO(Registration ID:CRD42020185008),we identified relevant controlled in vivo studies published in English by searching the PubMed,Web of Science,and Embase databases.No restrictions of the year of publication were applied and the last literature search was conducted on August 3,2020.We then conducted a random-effects meta-analysis using the restricted maximum likelihood estimator.A total of 71 studies met our inclusion crite ria and were included in the systematic review.Our results showed that overall,gene therapies were associated with improvements in locomotor score(standardized mean difference[SMD]:2.07,95%confidence interval[CI]:1.68-2.47,Tau^(2)=2.13,I^(2)=83.6%)and axonal regrowth(SMD:2.78,95%CI:1.92-3.65,Tau^(2)=4.13,I^(2)=85.5%).There was significant asymmetry in the funnel plots of both outcome measures indicating the presence of publication bias.We used a modified CAMARADES(Collaborative Approach to M eta-Analysis and Review of Animal Data in Experimental Studies)checklist to assess the risk of bias,finding that the median score was 4(IQR:3-5).In particula r,reports of allocation concealment and sample size calculations were lacking.In conclusion,gene therapies are showing promise as therapies for spinal co rd injury repair,but there is no consensus on which gene or genes should be targeted.
