scholarly journals Gene therapy: advances, challenges and perspectives

2017 ◽  
Vol 15 (3) ◽  
pp. 369-375 ◽  
Author(s):  
Giulliana Augusta Rangel Gonçalves ◽  
Raquel de Melo Alves Paiva
Keyword(s):  
Gene Therapy ◽  
Germ Line ◽  
Genetic Material ◽  
The United States ◽  
In Vivo Studies ◽  
Basic Unit ◽  
Target Cells ◽  
Site Specific ◽  
Genomic Editing

ABSTRACT The ability to make site-specific modifications to the human genome has been an objective in medicine since the recognition of the gene as the basic unit of heredity. Thus, gene therapy is understood as the ability of genetic improvement through the correction of altered (mutated) genes or site-specific modifications that target therapeutic treatment. This therapy became possible through the advances of genetics and bioengineering that enabled manipulating vectors for delivery of extrachromosomal material to target cells. One of the main focuses of this technique is the optimization of delivery vehicles (vectors) that are mostly plasmids, nanostructured or viruses. The viruses are more often investigated due to their excellence of invading cells and inserting their genetic material. However, there is great concern regarding exacerbated immune responses and genome manipulation, especially in germ line cells. In vivo studies in in somatic cell showed satisfactory results with approved protocols in clinical trials. These trials have been conducted in the United States, Europe, Australia and China. Recent biotechnological advances, such as induced pluripotent stem cells in patients with liver diseases, chimeric antigen receptor T-cell immunotherapy, and genomic editing by CRISPR/Cas9, are addressed in this review.

scholarly journals Vector-mediated cancer gene therapy: A review

2020 ◽  
Vol 13 (2) ◽  
pp. 152-165
Author(s):  
Manisha. B. Shinde ◽  
Dr. Archana D. Kajale ◽  
Dr. Madhuri A. Channawar ◽  
Dr. Shilpa R. Gawande
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Nuclear Translocation ◽  
Ex Vivo ◽  
Gene Knockout ◽  
Genetic Material ◽  
Target Cells ◽  
Human Beings ◽  
Vector Systems

Gene therapy is the transfer of genetic material to cure a disease or at least to improve the clinical status of a patient. One of the basic concepts of gene therapy is to transform viruses into genetic shuttles, which will deliver the gene of interest into the target cells. Safe methods have been devised to do this, using several viral and non-viral vectors. Two main approaches emerged: in vivo modification and ex vivo modification. Retrovirus, adenovirus, adenoassociated virus are suitable for gene therapeutic approaches which are based on permanent expression of the therapeutic gene. Non-viral vectors are far less efficient than viral vectors, but they have advantages due to their low immunogenicity and their large capacity for therapeutic DNA. The most commonly used DNA virus vectors are based on adenoviruses and adeno-associated viruses. An example of gene-knockout mediated gene therapy is the knockout of the human CCR5 gene in T-cells in order to control HIV infection. To improve the function of non-viral vectors, the addition of viral functions such as receptor mediated uptake and nuclear translocation of DNA may finally lead to the development of an artificial virus. Gene transfer protocols have been approved for human use in inherited diseases, cancers and acquired disorders. Although the available vector systems are able to deliver genes in vivo into cells, the ideal delivery vehicle has not been found. Thus, the present viral vectors should be used only with great caution in human beings and further progress in vector development is necessary.

Non-Viral Vectors for Gene Delivery

2018 ◽  
Vol 9 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Aparna Bansal ◽  
Himanshu
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Expression System ◽  
Target Cells ◽  
Specific Expression ◽  
Naked Dna

Introduction: Gene therapy has emerged out as a promising therapeutic pave for the treatment of genetic and acquired diseases. Gene transfection into target cells using naked DNA is a simple and safe approach which has been further improved by combining vectors or gene carriers. Both viral and non-viral approaches have achieved a milestone to establish this technique, but non-viral approaches have attained a significant attention because of their favourable properties like less immunotoxicity and biosafety, easy to produce with versatile surface modifications, etc. Literature is rich in evidences which revealed that undoubtedly, non–viral vectors have acquired a unique place in gene therapy but still there are number of challenges which are to be overcome to increase their effectiveness and prove them ideal gene vectors. Conclusion: To date, tissue specific expression, long lasting gene expression system, enhanced gene transfection efficiency has been achieved with improvement in delivery methods using non-viral vectors. This review mainly summarizes the various physical and chemical methods for gene transfer in vitro and in vivo.

scholarly journals Photosensitizing Medications and Skin Cancer: A Comprehensive Review

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2344
Author(s):  
Elisabeth A. George ◽  
Navya Baranwal ◽  
Jae H. Kang ◽  
Abrar A. Qureshi ◽  
Aaron M. Drucker ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Cancer Risk ◽  
Cell Carcinoma ◽  
The United States ◽  
In Vivo Studies ◽  
Cancer Risk Factors ◽  
Skin Cancer Risk ◽  
Number Of Patients

(1) The incidence of skin cancer is increasing in the United States (US) despite scientific advances in our understanding of skin cancer risk factors and treatments. In vitro and in vivo studies have provided evidence that suggests that certain photosensitizing medications (PSMs) increase skin cancer risk. This review summarizes current epidemiological evidence on the association between common PSMs and skin cancer. (2) A comprehensive literature search was conducted to identify meta-analyses, observational studies and clinical trials that report on skin cancer events in PSM users. The associated risks of keratinocyte carcinoma (squamous cell carcinoma and basal cell carcinoma) and melanoma are summarized, for each PSM. (3) There are extensive reports on antihypertensives and statins relative to other PSMs, with positive and null findings, respectively. Fewer studies have explored amiodarone, metformin, antimicrobials and vemurafenib. No studies report on the individual skin cancer risks in glyburide, naproxen, piroxicam, chlorpromazine, thioridazine and nalidixic acid users. (4) The research gaps in understanding the relationship between PSMs and skin cancer outlined in this review should be prioritized because the US population is aging. Thus the number of patients prescribed PSMs is likely to continue to rise.

Antitumoural hydroxyapatite nanoparticles-mediated hepatoma-targeted trans-arterial embolization gene therapy: in vitro and in vivo studies

2012 ◽  
Vol 32 (6) ◽  
pp. 998-1007 ◽  
Author(s):  
Gaopeng Li ◽  
Lu Ye ◽  
Jingsheng Pan ◽  
Miaoyun Long ◽  
Zizhuo Zhao ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Arterial Embolization ◽  
In Vivo Studies ◽  
Hydroxyapatite Nanoparticles

Potential strategies for cancer gene therapy

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Gene Therapy ◽  
Clinical Stage ◽  
Genetic Material ◽  
Direct Methods ◽  
Cancer Gene Therapy ◽  
Target Cells ◽  
Target Tissue ◽  
Cancer Gene ◽  
P Gene

Gene therapy involves transferring genetic material (DNA or RNA) to repair, regulate or replace genes to cure a disease. One of the most crucial barriers is successful delivery of the targeted gene into the target tissue. Various vector-based approaches have been developed to deliver the transgene to the target cells. In different cancers, numerous of these vectors are being developed for purposes such as immunotherapy, suicide gene therapy, microRNA (miRNA) focused treatment, oncogene silencing, and gene editing using CRISPR/Cas9. This article reviews several alternatives to cancer gene therapy, as well as their preclinical and clinical outcomes, possible limitations, and overall therapy effects. Ways of delivering cancer gene therapy include direct methods for introducing genetic material. Nonviral vectors are easy to manufacture and may be chemically modified to increase their usefulness. Cationic polymers such as Poly-L-Lysine (PLL) and Polyethylenimine (PEI-SS) are the most extensively used polycationic polymers for gene transfer, particularly in vitro. Many RNAi-based therapeutic approaches are approaching the clinical stage, and nanocarriers are likely to play a crucial role in treating specific cancers. In the previous decade, non-viral approaches were used in more than 17 percent of all gene therapy trials. The message is that this is a safe and effective technique for transferring genes to cancer patients who need it to be a safe, successful therapy. Exosomes were developed to carry oncogene-specific short interfering RNA. Sushrut and colleagues revealed that exosomes provide superior carriers of short RNA and prevent tumor growth than liposomes. Inhalation-based gene therapy (aerosol-mediated gene delivery) has gained pace as a feasible treatment approach, especially for lung cancer. Because the intended transgene is steered to specific cells/tissues, this should further increase therapeutic efficiency.

How Does the Selection of Laboratory Mice Affect the Results of Physiological Distribution of Radiopharmaceuticals?

2021 ◽  
Vol 14 ◽  
Author(s):  
Urszula Karczmarczyk ◽  
Piotr Ochniewicz ◽  
Ewa Laszuk ◽  
Kamil Tomczyk ◽  
Piotr Garnuszek
Keyword(s):  
Quality Control ◽  
Statistical Significance ◽  
The United States ◽  
Radioactive Isotopes ◽  
In Vivo Studies ◽  
P Value ◽  
Preclinical Studies ◽  
In Vivo Experiments ◽  
Physicochemical Methods

Background: The choice of mice strain can significantly influence the physiological distribution and may lead to an inadequate assessment of the radiopharmaceutical properties. Objective: This work aims to present how the legal requirements that apply to radiopharmaceuticals contained in the various guidelines determine the choice of the mouse strain for quality control and preclinical studies and affect the results of physiological distribution. Methods: Swiss and BALB/c mice were chosen as commonly used strains in experiments for research and quality control purposes. Radiopharmaceuticals, i.e., preparations containing one or more radioactive isotopes in their composition, are subject to the same legal regulations at every stage of the research, development and routine quality control as all other medicines. Therefore, in vivo experiments are to be carried out to confirm the pharmacological properties and safety. Moreover, if a radiopharmaceutical's chemical structure is unknown or complex and impossible to be determined by physicochemical methods, an analysis of physiological distribution in a rodent animal model needs to be performed. Results: In our studies, thirty-six mice (Swiss n=18, BALB/c n=18) were randomly divided into six groups and injected with the following radiopharmaceuticals: [99mTc]Tc-Colloid, [99mTc]Tc-DTPA and [99mTc]Tc-EHIDA. Measurement of physiological distribution was conducted following the requirements of European Pharmacopoeia (Ph. Eur.) monograph 0689, internal instructions and the United States Pharmacopeia (USP) monograph, respectively. Additionally, at preclinical studies, ten mice (Swiss n=5, BALB/c n=5) were injected with the new tracer [99mTc]Tc-PSMA-T4, and its physiological distribution has been compared. The p-value <0.05 proved the statistical significance of the radiopharmaceutical physiological distribution. Conclusion: We claim that mice strain choice can significantly influence the physiological distribution and may lead to inaccurate quality control results and incomprehensible interpretation of the results from preclinical in vivo studies of a new radiopharmaceutical.

Abstract 543: Clinical Development of Cardiac Reprogramming Gene Therapy

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Huanyu Zhou ◽  
Laura M Lombardi ◽  
Christopher A Reid ◽  
Jin Yang ◽  
Chetan Srinath ◽  
...  
Keyword(s):  
Heart Failure ◽  
Gene Therapy ◽  
Clinical Application ◽  
Cardiac Fibroblasts ◽  
Target Cells ◽  
Large Animal ◽  
Safety And Efficacy ◽  
Treat Heart Failure ◽  
Ability To Regenerate

Heart failure affects an estimated 38 million people worldwide and is typically caused by cardiomyocyte (CM) loss or dysfunction. Although CMs have limited ability to regenerate, a large pool of non-myocytes, including cardiac fibroblasts (CFs), exist in the postnatal heart. In vivo reprogramming of non-myocytes into functional CMs is emerging as a potential new approach to treat heart failure and substantial proof-of-concept has been achieved in this new field. However, challenges remain in terms of clinical application. First, reported human reprogramming cocktails often consist of five to seven factors that require multiple AAV vectors for delivery. Thus, a less complex cocktail that is able to fit into one AAV vector is needed for this technology to impact human health. Second, the lack of specificity in AAV tropism further complicates the safety and regulatory landscape. A means to limit the expression of reprogramming factors to target cells is critical for maximizing long-term safety. Lastly, although promising studies in small animals have already been reported, safety and efficacy results in large animal MI models are critical to justify cardiac reprogramming in human clinical trials. We have developed a novel human cardiac reprogramming cocktail that consists of only two transcription factors and one miRNA. This new cocktail has been engineered into a single AAV cassette to efficiently reprogram human CFs into cardiomyocytes. We also substantially improved transduction of hCFs through AAV capsid engineering and eliminated CMs expression through a microRNA de-targeting method. Moreover, our novel cardiac reprogramming gene therapy improved cardiac function in both rat and swine MI models upon delivery at various time-points after MI without inducing arrhythmias. Given these promising safety and efficacy results in larger animals, we endeavor to translate direct cardiac reprogramming for clinical application.

scholarly journals Baculoviruses as Vectors for Gene Therapy against Human Prostate Cancer

2003 ◽  
Vol 2003 (2) ◽  
pp. 79-91 ◽  
Author(s):  
Lindsay J. Stanbridge ◽  
Vincent Dussupt ◽  
Norman J. Maitland
Keyword(s):  
Prostate Cancer ◽  
Gene Therapy ◽  
Viral Entry ◽  
Mammalian Cells ◽  
Primary Tumour ◽  
Genetic Material ◽  
Cell Types ◽  
Attractive Alternative

Current curative strategies for prostate cancer are restricted to the primary tumour, and the effect of treatments to control metastatic disease is not sustained. Therefore, the application of gene therapy to prostate cancer is an attractive alternative. Baculoviruses are highly restricted insect viruses, which can enter, but not replicate in mammalian cells. Baculoviruses can incorporate large amounts of extra genetic material, and will express transgenes in mammalian cells when under the control of a mammalian or strong viral promoter. Successful gene delivery has been achieved both in vitro and in vivo and into both dividing and nondividing cells, which is important since prostate cancers divide relatively slowly. In addition, the envelope protein gp64 is sufficiently mutable to allow targeted transduction of particular cell types. In this review, the advantages of using baculoviruses for prostate cancer gene therapy are explored, and the mechanisms of viral entry and transgene expression are described.

scholarly journals In Vitro Models, Standards, and Experimental Methods for Tobacco Products

2019 ◽  
Vol 30 (1) ◽  
pp. 16-21 ◽  
Author(s):  
T. Aghaloo ◽  
J.J. Kim ◽  
T. Gordon ◽  
H.P. Behrsing
Keyword(s):  
Cigarette Smoking ◽  
Electronic Cigarettes ◽  
Testing Machine ◽  
The United States ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Tobacco Products ◽  
Direct Exposure

Traditional tobacco products have well-known systemic and local oral effects, including inflammation, vasoconstriction, delayed wound healing, and increased severity of periodontal disease. Specifically in the oral cavity and the lung, cigarette smoking produces cancer, increased infectivity, acute and chronic inflammation, changes in gene expression in epithelial lining cells, and microbiome changes. In recent years, cigarette smoking has greatly decreased in the United States, but the use of new tobacco products has gained tremendous popularity. Without significant knowledge of the oral sequelae of products such as electronic cigarettes, researchers must evaluate current in vitro and in vivo methods to study these agents, as well as develop new tools to adequately study their effects. Some in vitro testing has been performed for electronic cigarettes, including toxicologic models and assays, but these mostly study the effect on the respiratory tract. Recently, direct exposure of the aerosol to in vitro 3-dimensional tissue constructs has been performed, demonstrating changes in cell viability and inflammatory cytokines. For in vivo studies, a universal e-cigarette testing machine or standard vaping regime is needed. A standard research electronic cigarette has recently been developed by the National Institute of Drug Abuse, and other devices delivering aerosols with different nicotine concentrations are becoming available. One of the biggest challenges in this research is keeping up with the new products and the rapidly changing technologies in the industry.

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