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In 2016,the world's first birth by mitochondrial replacement technology was born.In 2017,UK Human Fertilisation & Embryology Authority approved the first application by Newcastle Fertility at Life for the use of mitochondrial replacement to treat patients.The technology has aroused controversy over gene modification of hu-man reproductive system,and some scholars have expressed their concerns and objections from the perspective of ethics.This paper would respond to these ethical concerns from three aspects of technical security,reproductive system gene modification and parenthood,oppose to call the technique of mitochondria replacement as the term"three parent test-tube baby technology",and clear that the application of mitochondrial replacement technology can be justified by ethics on the premise of ensuring safety and effectiveness.
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The CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) system was first identified in bacteria and archaea and can degrade exogenous substrates. It was developed as a gene editing technology in 2013. Over the subsequent years, it has received extensive attention owing to its easy manipulation, high efficiency, and wide application in gene mutation and transcriptional regulation in mammals and plants. The process of CRISPR/Cas is optimized constantly and its application has also expanded dramatically. Therefore, CRISPR/Cas is considered a revolutionary technology in plant biology. Here, we introduce the mechanism of the type II CRISPR/Cas called CRISPR/Cas9, update its recent advances in various applications in plants, and discuss its future prospects to provide an argument for its use in the study of medicinal plants.
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Genetically modified tool animal models are the animal models,which are generated by modifying a defined gene and can be used as a tool to help realize other objective.Genetically modified large animals have wide applications in agriculture and biomedicine.Tool animal models play important role in biological research and development of new drugs in biomedicine,especially,have made tremendous contribution in revealing gene function and pathway of signal transduction.Pigs are not only an economically important agriculture animals,but also an ideal animal model in biomedicine due to its close similarity to human in physiology,as well as organ structure and size.Thanks to the breakthrough of newly emerged gene editing technology,striking progress has made in establishment of genetically modified tool pig models which include the ones used for monitoring pluripotency of cells,tracing cell lineages,replacing genes mediated by Cre recombinase,mimicking immunodeficiency,as well as gene editing in vivo.These tool models have been widely applied in biological research.Here,we will review the progress in generation of genetically modified tool pig models and their applications.
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The established immunodeficient animal models could be used as valuable resource for mechanism re-search of related disease in humans, drug discovery and development, translational research and stem cell research.How-ever, it is difficult and low-efficient to establish the genetic modified animal models using traditional technologies.The re-ports for immunodeficient animal models are few in middle-size and large animals.Recently, several effective gene-targeting tools, including ZFNs, TALENs, CRISPR/Cas9, develop quickly and provide technology basis for the establishment of im-munodeficient animal models.In this paper, the technology principles and research progresses of ZFNs, TALENs, CRISPR/Cas9 are introduced.The significant progresses of these emerging technologies achieved in immunodeficient ani-mal models are also elaborated, including KO Rag1/Rag2 rabbit, KO Rag1/Rag2 pig, KO IL2rg pig, KO Ppar-g/Rag1 monkey, and so on.In addition to being models for researching SCID-related diseases in humans, and evaluating the effica-cy and safety of stem-cell engraftment, these models may be also useful to develop surgical procedures for placement of grafts before clinical trials in humans, to produce humanized animals and bridge the gap between laboratory animal and medicical research.The immunodeficient animal models described here represent a step toward the comprehensive evalua-tion of preclinical cellular regenerative strategies.
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Objective We want to study the therapeutic efficiency of autologous ADMSC transplantation in myocardial infarction.And we try to find out a good way to improve the therapeutic efficiency by using the combination of gene therapy and cell therapy.Anti-apoptotic protein XIAP was selected to fight against the ischemic environment of myocardic infaction.Methods ADMSC was isolated from rat inguinal fat tissue.ADMSC was cultivated with DMEM.XIAP experession plasmid was elertco-transduced to ADMSC.The anti-apototic function of XIAP was tested by serum stavation induced apotosis.The method of ligation of the left anterior descending artery was used to prepare the Myocardial infarction model.Then rats were randomly separated into three groups to receive direct epicardial injections of normal saline,or ADMSCs cell suspension or XIAP modified ADMSCs cell suspension at five sites in central zones of myocardial infarction and border zone.Cardiac function and the infarct size were evaluated 4 weeks after ADMSCs transplantation.Results West blotting suggest that,XIAP over-expression block serum starvation induced apotosis.It showed that there are significant statistic difference among XIAP modified ADMSC transplantation group,ADMSC transplantation group and control group 4 weeks after myocardial infarction (P ＜ 0.05).Left ventricular ejection fraction(LVEF) showed a significant improvement in ADMSCs transplantation group compared to control group (P ＜0.05).Left ventricular end systolic diameter(LVDs) and left ventricular end diastolic diameter(LVDd) of ADMSCs group were smaller than control group(P ＜ 0.05).The area of myocardial infarction was significantly reduced in the ADMSCs transplantation group compared to the saline group(P ＜0.05).Compared to ADMSCs transplantation group,effect of the XIAP modified ADMSC in rats with myocardial infarction is more obvious.The reduction of LVEF of XIAP modified ADMSCs group was signific antly lower(9％) than the ADMSCs group(16％) (P ＜ 0.01).Infarction area in XIAP modified ADMSCs group(3.26 ±0.95)％ was smaller than ADMSCs group(5.17 ±2.03)％ (P ＜0.05).Conclusion Autologus ADMSC transplantation is an efficient therapeutic tool in myocardial infarction therapy.Over expression of XIAP can partly inhibit lowserum induced apotosis of ADMSC in vitro,and it can improve left ventricular function better in vivo.Over expression XIAP of ADMSC can improve the therapeutic efficiency compare to ADMSC transplantation.
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Although adoptive T cell therapy (ACT) has become a promising immunotherapeutic regime for cancer treatment, its effectiveness has been hindered by several inherent shortcomings regarding safety and efficacy. During the past few decades, several strategies for enhancing the efficacy of ACT have been developed and introduced in clinic. This review will summarize not only the past approaches but also the latest strategies which have been shown to enhance the anticancer activity of ACT.
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Inmunoterapia , Tratamiento Basado en Trasplante de Células y TejidosRESUMEN
Objective To observe the toxicity and adverse reaction of interleukin(IL) 2 gene modified allogenic gastric cancer cell line in far advanced gastric cancer patients. Methods A phase Ⅰ clinical trial was conducted for sixteen far advanced gastric cancer patients with IL 2 gene modified gastric cancer cell line. By gene recombinant technique, human IL 2 cDNA was transfected into human gastric cancer cell line MKN45 via retrovirus based vector.These cells were then inactivated by irradiation (100 Gy) and were cryopreserved for the vaccine. The immunization were administrated subcutaneously at the first, 8 th , 15 th , 29 th and 58 th day. The patients were divided into 4 dosage groups, which the dosage of the vaccine was administrated in each subsequent level. The toxicity and adverse reaction were evaluated by WHO criteria. Results Fifteen of the 16 patients completed the immunization. Side effects of treatment consisted of mild to moderate fever, redness and swelling at the site of injection, which were the most common symptoms. Only one patient abandoned after the third injection due to rapidly progressive disease. Other reactions including allergic shock, bone marrow depression and disturbance of hepatorenal function were not observed during the immunization.In some patients, the serum transferrin, humoral immune parameters such as IgG, IgA, IgM,IL 2 and cellular immune parameters such as CD + 3,CD + 4,CD + 8 had been improved after treatment.Conclusions This trial demonstrates the feasibility, safety and potential therapeutic effects of vaccination of gastric cancer patients with allogenic, gene modified gastric cancer cell line. The dosage of the vaccine recommended for phase Ⅱ clinical trail is 5?10 7 cells per time.
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Objective To observe the changes of the gene expressions at spinal cord injury site of rat after transplantation of BDNF genetically modified neural stem cells(NSCs) so as to provide basic data for the repair of spinal cord injury. Methods The Wistar rats were randomly divided into 4 groups: control group, operation group, NSCs transplantation group, BDNF NSCs transplantation group. Four time points(7 day, 1 month, 2 month, 3 month) were divided for each group. The expressions of ? galactosidase and BDNF, GFAP, NF 200 at the site of spinal cord injury were observed by cell transplantation, X gal histochemistry, immunocytochemistry, in situ hybridization, etc. Results After transplantation of BDNF genetically modified NSCs, some X gal positive cells were found at the sections of spinal cord injury. The expressions of BDNF were strong, especially at 1 week and 1 month post transplantation in transplantation group. The GFAP and NF 200 positive cells were also found at each time point in each group. Conclusion BDNF genetically modified NSCs can survive at the site of spinal cord injury and can strongly express BDNF, suggesting that BDNF genetically modified NSCs can be used as the material for the repair of spinal cord injury.