基因治疗的载体系统及应用

目前的基因载体系统可分为病毒载体和非病毒载体。利用病毒载体介导的基因转移 ,以其高转染率和良好靶向性成为肿瘤基因治疗中应用最广泛的方法。非病毒载体由于其非免疫性和易于生产性而逐渐引起学者瞩目。基因治疗是一种用正常基因取代缺陷基因的治疗 ,目前主要用于肿瘤治疗 ,同时在基因治疗造血细胞疾病、心血管疾病、风湿性关节炎方面 ,已在动物试验中取得一定进展。1　基因载体系统本文介绍几种将外源基因引入宿主细胞的转移方法 ,这些方法可使外源基因短期 (数天 )或长期 (数星期或数年 )稳定的表达[1] 。通常可将这些方法分为病毒载…     

基因治疗现状与前景

基因治疗是一种新的治疗手段.临床上用于治疗多种疾病,癌症是其主要应用领域.过去十年,基因治疗研究发展迅猛,取得了很大的进步,部分基因治疗方案已进入临床试验阶段.但也遇到了很多困难,如其靶向性,转移效率较低等问题亟待解决,其安全性更是长期困扰着人们.基因治疗要能将外源遗传物质靶向性地导入到特异的细胞,要有安全和高效的基因导入系统,有等研究者更多的探索.本文结合近年来基因治疗的基础及临床研究,对基因治疗的载体及治疗策略、主要成就、存在问题等方面进行了综述.     

聚乙烯亚胺纳米基因递送系统的研究进展

基因治疗在恶性肿瘤、感染性疾病、自身免疫性疾病、罕见病等重大难治性疾病的治疗中表现出巨大潜力。基因递送载体是基因治疗能否成功实施的关键所在,聚乙烯亚胺（PEI）是一种被广泛研究的阳离子基因递送载体,在不同细胞系和转染条件下均展现出稳定高效的基因转染效果,其中PEI25k更被视作基因转染的“黄金标准”。为解决PEI在基因递送中存在的体内转染效率低、细胞毒性大、靶向性低和负载基因溶酶体降解等问题,该文对基于PEI设计构建新型纳米递送系统用于基因治疗的研究进展进行综述,主要包括高相对分子质量线性PEI、多糖、亲水性的聚合物和右旋糖酐修饰的PEI,交联的低相对分子质量PEI,基于PEI的无机纳米递送载体以及基于PEI的药物与基因共递送载体系统,以期为进一步构建高效低毒的基因递送系统提供理论指导。     

以纳米颗粒为载体转染基因的发展概况

目的综述以纳米颗粒作为基因载体进行基因治疗的发展概况。方法依据国内外刊物公开发表的文献,对有关以纳米颗粒作为基因递送载体进行基因治疗的研究进行分类、归纳与整理。结果纳米颗粒转运系统能够保护被转运的基因,有较高的转染效率,具有良好的靶向性,并且提高了药物的生物利用度,显示出一定的缓控释作用。结论纳米颗粒作为基因递送载体具有广阔的发展前景。     

基因治疗产品及其载体的研究进展和挑战

基因治疗是一种通过改变个体的基因表达来治疗疾病的方法，为肿瘤、罕见病及其他难治性疾病提供了全新的治疗策略。基因治疗通过基因编辑技术实现对个体致病基因的改造，同时也依赖基因递送载体改善其在体内的稳定性和靶向性。本综述简述了基因治疗的方式，结合目前的基因治疗产品，介绍了病毒、非病毒基因递送载体和基因编辑技术在基因治疗中的发展概况，并总结归纳了临床实践中基因治疗的安全性问题。     

肝癌靶向基因治疗载体研究进展

<正>目前对于肝癌治疗的研究已经进入分子水平,随着分子生物学的快速发展和基因工程技术的日臻成熟,肝癌的基因治疗已经迅速发展成为继手术切除、放化疗和介入治疗之后一个新的治疗模式。虽然已有许多将目的基因转入活细胞的方法,但仍存在转移效率不高、靶向性不高的问题。因此寻求一种高靶向性、高转染率的方法已成为研究肝癌靶向基因治疗的热点。在肝癌靶向基因治疗过程中,目前常用的治疗基因转移方法主要包括病毒载体和非     

一种新的药物传递系统——超声微泡剂

目的：探讨超声微泡剂作为药物载体传输药物的机制及临床应用前景。方法：查阅国内外文献，进行归纳总结，分析其作用机制及应用前景。结果：超声微泡剂可作为药物载体，可传输基因和药物，能提高基因的转染率和表达，配合超声处理产生的空化效应可提高细胞膜的通透性，利于药物穿透；并且具有靶向性。因此在基因治疗和抗肿瘤治疗方面有很好的应用前景。结论：随着超声技术和微泡剂制备技术的发展，超声微泡剂必将为临床治疗提供一种安全、高效、无创的超声介导靶向传输及治疗系统。     

肝细胞癌的靶向基因治疗

靶向基因治疗技术的发展和应用为肝癌治疗提供了新的手段，具备广阔的临床应用前景。基因治疗必需具备遗传物质和目的基因载体两个条件。载体分为病毒载体和外病毒载体，而遗传物质则可根据相应的治疗目的加以选择。     

纳米药物在青光眼治疗中的研究进展

目的:了解纳米药物在青光眼治疗中的应用进展。方法:查阅近年来国内外相关文献,从降眼压、保护视神经和抗纤维化等作用方面对治疗青光眼的纳米药物的研究进行归纳和总结。结果与结论:纳米药物有角结膜透过率高、眼表作用时间长、长期缓释和靶向性好等优点,可有效解决青光眼药物治疗中的眼后节靶向给药和蛋白类药物长效释放等难题,并减少防腐剂造成的眼表毒性。在保护视神经方面,纳米药物可以为基因或蛋白类药物提供高效载体,实现细胞靶向的缓控释给药。对于青光眼术后的抗纤维化治疗,纳米药物可显著降低药物的毒副作用,有效减少并发症的发生。以纳米药物为载体的青光眼基因治疗相对于病毒载体有着更好的安全性和有效性,展现出良好的应用前景。     

减毒沙门菌载体在肿瘤基因治疗中的研究进展

目前基因治疗发展迅速,肿瘤基因治疗方法已经逐步从实验及基础研究过渡到临床试用阶段,理论和技术层次上日趋成熟。然而基因治疗还没达到完全安全、高效、准确的目标,其中基因治疗的载体是最受关注问题之一。合适的载体应具备最大的有效性和最小的毒性,传统生物类载体主要是病毒载体和非病毒载体。目前低毒或无毒的且具有靶向性感染特点的细菌载体在肿瘤基因治疗得到证实,充分说明了细菌载体开辟抗肿瘤治疗的新途径。本文就减毒沙门菌作为载体在肿瘤基因治疗中的应用综述如下。     

Colloidal soft matter as drug delivery system

Growing interest is being dedicated to soft matter because of its potential in delivering any type of drugs. Since hydrophilic, lipophilic, small and big molecules can be loaded into these colloidal systems and administered through the parenteral or nonparenteral route, soft matter systems have been used to solve many biomedical and pharmaceutical problems. In fact, they make possible to overcome difficulties in the formulation and delivery of poorly water-soluble drug molecules, settle some stability issues typical of biological drug molecules, design parenteral sustained release forms and provide functionalized soft particles that are very effective in drug targeting. This review deals with the important role that colloids play in the drug delivery and targeting, with particular attention to the more currently used systems such as microemulsions, organogels, liposomes, micelles, and dendrimers. Though significant progress has been made in drug targeting, some challenges still remain. Further efforts will be required to better understand the characteristics of targets and to discover new ones. In-depth knowledge of the physico-chemical structure and properties of the systems used for targeting is fundamental for understanding the mechanism of interaction with the biological substrate and the consequent drug release.     

Destination Brain: the Past,Present, and Future of Therapeutic Gene Delivery

Neurological diseases and disorders (NDDs) present a significant societal burden and currently available drug- and biological-based therapeutic strategies have proven inadequate to alleviate it. Gene therapy is a suitable alternative to treat NDDs compared to conventional systems since it can be tailored to specifically alter select gene expression, reverse disease phenotype and restore normal function. The scope of gene therapy has broadened over the years with the advent of RNA interference and genome editing technologies. Consequently, encouraging results from central nervous system (CNS)-targeted gene delivery studies have led to their transition from preclinical to clinical trials. As we shift to an exciting gene therapy era, a retrospective of available literature on CNS-associated gene delivery is in order. This review is timely in this regard, since it analyzes key challenges and major findings from the last two decades and evaluates future prospects of brain gene delivery. We emphasize major areas consisting of physiological and pharmacological challenges in gene therapy, function-based selection of a ideal cellular target(s), available therapy modalities, and diversity of viral vectors and nanoparticles as vehicle systems. Further, we present plausible answers to key questions such as strategies to circumvent low blood-brain barrier permeability and most suitable CNS cell types for targeting. We compare and contrast pros and cons of the tested viral vectors in the context of delivery systems used in past and current clinical trials. Gene vector design challenges are also evaluated in the context of cell-specific promoters. Key challenges and findings reported for recent gene therapy clinical trials, assessing viral vectors and nanoparticles are discussed from the perspective of bench to bedside gene therapy translation. We conclude this review by tying together gene delivery challenges, available vehicle systems and comprehensive analyses of neuropathogenesis to outline future prospects of CNS-targeted gene therapies.     

Polymeric micelles as nanocarriers for drug delivery

Polymeric micelles are built from amphiphilic polymers through self-assembly effects. Due to their unique core shell structure, small size and modifiable surface, polymeric micelles have been widely investigated as nanoscale drug delivery carriers. Such systems may increase drug solubility and have possible applications in tumour targeting and gene therapy. These biomedical applications require that polymeric micelles are biocompatible, have prolonged blood circulation and possess high drug-loading efficiency. In addition, tumour targeting and smart drug release behaviour need special modification towards micelles with multiplicate functional substances. This review focuses on the present progress of polymeric micelles and highlights some critical issues for their application in drug delivery systems. Composition and micellisation procedures are also briefly discussed.     

Thermo-responsive systems for controlled drug delivery

Controlled drug delivery systems represent advanced systems that can be tightly modulated by stimuli in order to treat diseases in which sustained drug release is undesirable. Among the many different stimuli-sensitive delivery systems, temperature-sensitive drug delivery systems offer great potential over their counterparts due to their versatility in design, tunability of phase transition temperatures, passive targeting ability and in situ phase transitions. Thus, thermosensitive drug delivery systems can overcome many of the hurdles of conventional drug delivery systems in order to increase drug efficacies, drug targeting and decrease drug toxicities. In an effort to further control existing temperature-responsive systems, current innovative applications have combined temperature with other stimuli such as pH and light. The result has been the development of highly sophisticated systems, which demonstrate exquisite control over drug release and represent huge advances in biomedical research.     

Thermo-responsive systems for controlled drug delivery

Controlled drug delivery systems represent advanced systems that can be tightly modulated by stimuli in order to treat diseases in which sustained drug release is undesirable. Among the many different stimuli-sensitive delivery systems, temperature-sensitive drug delivery systems offer great potential over their counterparts due to their versatility in design, tunability of phase transition temperatures, passive targeting ability and in situ phase transitions. Thus, thermosensitive drug delivery systems can overcome many of the hurdles of conventional drug delivery systems in order to increase drug efficacies, drug targeting and decrease drug toxicities. In an effort to further control existing temperature-responsive systems, current innovative applications have combined temperature with other stimuli such as pH and light. The result has been the development of highly sophisticated systems, which demonstrate exquisite control over drug release and represent huge advances in biomedical research.     

Recent Perspectives in Ocular Drug Delivery

Anatomy and physiology of the eye makes it a highly protected organ. Designing an effective therapy for ocular diseases, especially for the posterior segment, has been considered as a formidable task. Limitations of topical and intravitreal route of administration have challenged scientists to find alternative mode of administration like periocular routes. Transporter targeted drug delivery has generated a great deal of interest in the field because of its potential to overcome many barriers associated with current therapy. Application of nanotechnology has been very promising in the treatment of a gamut of diseases. In this review, we have briefly discussed several ocular drug delivery systems such as microemulsions, nanosuspensions, nanoparticles, liposomes, niosomes, dendrimers, implants, and hydrogels. Potential for ocular gene therapy has also been described in this article. In near future, a great deal of attention will be paid to develop non-invasive sustained drug release for both anterior and posterior segment eye disorders. A better understanding of nature of ocular diseases, barriers and factors affecting in vivo performance, would greatly drive the development of new delivery systems. Current momentum in the invention of new drug delivery systems hold a promise towards much improved therapies for the treatment of vision threatening disorders. All the authors contributed equally to this work.     

Nanoparticle-Based Delivery of CRISPR/Cas9 Genome-Editing Therapeutics

The recent progress in harnessing the efficient and precise method of DNA editing provided by CRISPR/Cas9 is one of the most promising major advances in the field of gene therapy. However, the development of safe and optimally efficient delivery systems for CRISPR/Cas9 elements capable of achieving specific targeting of gene therapy to the location of interest without off-target effects is a primary challenge for clinical therapeutics. Nanoparticles (NPs) provide a promising means to meet such challenges. In this review, we present the most recent advances in developing innovative NP-based delivery systems that efficiently deliver CRISPR/Cas9 constructs and maximize their effectiveness.     

New strategies for cancer gene therapy: Progress and opportunities

1. To date, cancer persists as one of the most devastating diseases worldwide. Problems such as metastasis and tumour resistance to chemotherapy and radiotherapy have seriously limited the therapeutic effects of existing clinical treatments.
2. To address these problems, cancer gene therapy has been developing over the past two decades, specifically designed to deliver therapeutic genes to treat cancers using vector systems. So far, a number of genes and delivery vehicles have been evaluated and significant progress has been made with several gene therapy modalities in clinical trials. However, the lack of an ideal gene delivery system remains a major obstacle for the successful translation of regimen to the clinic.
3. Recent understanding of hypoxic and necrotic regions within solid tumours and rapid development of recombinant DNA technology have reignited the idea of using anaerobic bacteria as novel gene delivery systems. These bacterial vectors have unique advantages over other delivery systems and are likely to become the vector of choice for cancer gene therapy in the near future.
4. Meanwhile, complicated tumour pathophysiology and associated metastasis make it hard to rely on a single therapeutic modality for complete tumour eradication. Therefore, the combination of cancer gene therapy with other conventional treatments has become paramount.
5. The present review introduces important cancer gene therapy strategies and major vector systems that have been studied so far with an emphasis on bacteria-mediated cancer gene therapy. In addition, exemplary combined therapies are briefly reviewed.     

脂质和聚合物载体作为mRNA递送系统的研究进展

信使核糖核酸（messenger ribonucleic acid,mRNA）作为一种非常有潜力的基因药物,在蛋白质替代疗法、疫苗、基因编辑等方面具有广阔的应用前景。而安全高效的mRNA递送系统是其临床转化成药的关键。脂质和聚合物载体因其结构多样、制备简便等优势,被广泛用于mRNA递送。两者均能有效负载mRNA并保护其不被降解,促进其被靶细胞摄取,快速逃逸并释放mRNA,提升mRNA递送效率。通过对不同类型脂质和聚合物载体在mRNA递送中研究进展进行综述,以期为后续设计新型mRNA递送载体提供思路及参考。     

Tumor microenvironment responsive drug delivery systems

Conventional tumor-targeted drug delivery systems (DDSs) face challenges, such as unsatisfied systemic circulation, low targeting efficiency, poor tumoral penetration, and uncontrolled drug release. Recently, tumor cellular molecules-triggered DDSs have aroused great interests in addressing such dilemmas. With the introduction of several additional functionalities, the properties of these smart DDSs including size, surface charge and ligand exposure can response to different tumor microenvironments for a more efficient tumor targeting, and eventually achieve desired drug release for an optimized therapeutic efficiency. This review highlights the recent research progresses on smart tumor environment responsive drug delivery systems for targeted drug delivery. Dynamic targeting strategies and functional moieties sensitive to a variety of tumor cellular stimuli, including pH, glutathione, adenosine-triphosphate, reactive oxygen species, enzyme and inflammatory factors are summarized. Special emphasis of this review is placed on their responsive mechanisms, drug loading models, drawbacks and merits. Several typical multi-stimuli responsive DDSs are listed. And the main challenges and potential future development are discussed.