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  • 简介:AbstractNucleic acid therapeutics, which involve transferring exogenous genes inside target cells, are a promising clinical treatment option that can regulate gene expression at the transcriptional or post-transcriptional level. Ideally, this kind of treatment modality will not lead to an unwanted immune response. Compared with traditional treatment methods, nucleic acid therapeutics can achieve prolonged and stable curative effects. As an emerging treatment method, nucleic acid therapeutics have played an increasingly important role in clinical settings for the treatment of various conditions, including infectious diseases, cancer, immune-related diseases, and monogenetic diseases. To date, a large number of clinical trials have been conducted, and more than 30 nucleic acid drugs have been approved, highlighting the strong potential of this approach in clinical practice. Diverse carriers are used to protect nucleic acids from being degraded and to help them reach their targets accurately. However, some carriers are known to cause negative effects on the release and expression of nucleic acid drugs as well as adverse effects such as allergic reactions and accumulation in the liver. Therefore, biosafety assessment of delivery systems before their application in clinical settings is critical. In this review, we describe different delivery systems for nucleic acid drugs and discuss their biosafety in both preclinical and clinical studies, with particular focus on the carriers themselves, drug administration method, and overall treatment of the disease.

  • 标签: Nucleic acid therapeutics Delivery system Biosafety Viral vector Lipid Carrier-free delivery
  • 简介:Peptidenucleicacids(PNAs)aresyntheticoligonucleotideswithchemicallymodifiedbackbones.PNAscanbindtobothDNAandRNAtargetsinasequence-specificmannertoformPNA/DNAandPNA/RNAduplexstructures.Whenboundtodouble-strandedDNA(dsDNA)targets,thePNAmoleculereplacesoneDNAstrandintheduplexbystrandinvasiontoformaPNA/DNA/PNA[or(PNA)2/DNA]triplexstructureandthedisplacedDNAstrandexistsasasinglestrandedD-loop.PNAhasbeenusedinmanystudiesasresearchtoolsforgeneregulationandgenetargeting.TheDloopsgeneratedfromthePNAbindinghavealsobeendemonstratedforitspotentialininitiatingtranscriptionandinducinggeneexpression.PNAprovidesapowerfultooltostudythemechanismoftranscriptionandaninnovativestrategytoregulatetargetgeneexpression.AnunderstandingofthePNA-mediatedgeneregulationwillhaveimportantclinicalimplicationsintreatmentofmanyhumandiseasesincludinggenetic,cancerous,andage-relateddiseases.

  • 标签: 缩氨酸核酸 PNA 基因 调控 表达 DNA
  • 简介:Sincethefailureoftraditionaltherapy,genetherapyusingfunctionalDNAsequenceandsmallRNA/DNAmolecules(oligonucleotide)hasbecomeapromisingavenueforcancertreatment.ThediscoveryofRNAmoleculeshasimpelledresearcherstoinvestigatesmallregulatoryRNAfromvariousnaturalandartificialsourcesanddetermineacogenttargetforcontrollingtumorprogression.SmallregulatoryRNAsareusedfortherapeuticsilencingofoncogenesandaberrantDNArepairresponsegenes.Despitetheiradvantages,therapiesbasedonsmallRNAsexhibitlimitationsintermsofstabilityoftherapeuticdrugs,precisionbaseddeliveryintissues,precision-basedintercellularandintracellulartargeting,andtumorheterogeneity-basedresponses.Inthisstudy,wesummarizethepotentialanddrawbacksofsmallRNAsinnucleicacidtherapeuticsforcancer.

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  • 简介:Peptidenucleicacid(PNA)isaDNAmimicthatwasoriginallydevelopedbyPeterENielsenin1991asareagentforsequence-specificrecognitionofdoublestranded(ds)DNAbyaconventionaltriplehelixtypeprinciple.

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  • 简介:Circulatingfreenucleicacids;cellfreeDNAandcirculatingmicro-RNA,arefoundintheplasmaofpatientswithhematologicandsolidmalignanciesatlevelshigherthanthatofhealthyindividuals.InpatientswithhematologicmalignancycellfreeDNAreflectstheunderlyingtumormutationalprofile,whilstmicro-RNAsreflectgeneticinterferencemechanismswithinatumorandpotentiallythesurroundingmicroenvironmentandimmuneeffectorcells.Thesecirculatingnucleicacidsofferapotentiallysimple,non-invasive,repeatableanalysisthatcanaidindiagnosis,prognosisandtherapeuticdecisionsincancertreatment.

  • 标签: 恶性肿瘤 血液系统 循环 核酸 游离 液体
  • 简介:AbstractThe pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to unprecedented social and economic disruption. Many nucleic acid testing (NAT) laboratories in China have been established to control the epidemic better. This proficiency testing (PT) aims to evaluate the participants’ performance in qualitative and quantitative SARS-CoV-2 NAT and to explore the factors that contribute to differences in detection capabilities. Two different concentrations of RNA samples (A, B) were used for quantitative PT. Pseudovirus samples D, E (different concentrations) and negative sample (F) were used for qualitative PT. 50 data sets were reported for qualitative PT, of which 74.00% were entirely correct for all samples. Forty-two laboratories participated in the quantitative PT. 37 submitted all gene results, of which only 56.76% were satisfactory. For qualitative detection, it is suggested that laboratories should strengthen personnel training, select qualified detection kits, and reduce cross-contamination to improve detection accuracy. For quantitative detection, the results of the reverse transcription digital PCR (RT-dPCR) method were more comparable and reliable than those of reverse transcription quantitative PCR (RT-qPCR). The copy number concentration of ORF1ab and N in samples A and B scattered in 85, 223, 50, and 106 folds, respectively. The differences in the quantitative result of RT-qPCR was mainly caused by the non-standard use of reference materials and the lack of personnel operating skills. Comparing the satisfaction of participants participating in both quantitative and qualitative proficiency testing, 95.65% of the laboratories with satisfactory quantitative results also judged the qualitative results correctly, while 85.71% of the laboratories with unsatisfactory quantitative results were also unsatisfied with their qualitative judgments. Therefore, the quantitative ability is the basis of qualitative judgment. Overall, participants from hospitals reported more satisfactory results than those from enterprises and universities. Therefore, surveillance, daily qualitiy control and standardized operating procedures should be strengthened to improve the capability of SARS-CoV-2 NAT.

  • 标签: Proficiency testing SARS-CoV-2 Nucleic acid testing Reference material Quality assessment Pseudovirus
  • 简介:在在甲醇的9-vinyladenine和嘧啶库胸腺嘧啶之间的有约束力的机制与紫外可见的spectrophotometric方法被学习。把学习基于这,用象一个模板分子的胸腺嘧啶,是的9-vinyladenine是的新奇功能的单体和diethylene乙二醇dimethacrylate新cross-linker,特定的diethylene乙二醇基于dimethacrylate的分子地印的聚合的膜在纤维素支持上被准备。然后,结果地聚合的膜形态学与扫描电子显微镜学被设想,它的permselectivity作为底层用胸腺嘧啶,uracil,cytosine,腺嘌和guanine被检验。这结果证明印与diethylene乙二醇dimethacrylate准备的聚合的膜比另外的nucleic酸底为模板分子胸腺嘧啶和它的最佳的模拟uracil展出了更高的运输能力。膜也比作为cross-linker与乙烯乙二醇dimethacrylate做的印的膜呈现了更高的permselectivity。包括五nucleic酸的混合物什么时候基于胸腺嘧啶,uracil,cytosine,腺嘌和guanine,通过了diethylene乙二醇基于dimethacrylate的印胸腺嘧啶的聚合的膜,为模板分子胸腺嘧啶和它的最佳的模拟uracil的膜的识别被表明。因为它的高选择,作为cross-linker与diethylene乙二醇dimethacrylate准备的分子地印的膜可能对DNA的绝对hydrolysates的胸腺嘧啶试金或在生物样品的RNA的绝对hydrolysates的uracil试金适用,这被预言。

  • 标签: 乙二醇 选择性 胸腺嘧啶 渗透性 杂环化合物
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  • 简介:Thispaperanalyzesnanobridgetestswithconsiderationofadhesivecontactdeformation,whichoccursbetweenaprobetipandatestednanobeam,anddeformationofasubstrateortemplatethatsupportsthetestednanobeam.Analyticaldisplacement-loadrelation,includingadhesivecontactdeformationandsubstratedeformation,ispresentedhereforsmalldeformationofbending.Theanalyticresultsareconfirmedbyfiniteelementanalysis.Ifadhesivecontactdeformationandsubstratedeformationarenotconsideredintheanalysisofnanobridgetestdata,theymightleadtolowervaluesofYoung'smodulusoftestednanobeams.

  • 标签: 测试数据分析 接触变形 试验 有限元分析 弯曲变形 杨氏模量
  • 简介:Inthispapersomediscussionsshownwhatshouldbetheconsiderablereasonsfordifficultyincomparisonbetweenresultsofcavitationtestsinvacuumtankandsomesuggestionsaregivenhowtoimprovethecavitationtestsunderaconditionofvacuumpressure.

  • 标签: CAVITATION VACUUM TANK SCALE EFFECTS