Substance P Containing Peptide Gene Delivery Vectors for Specifically Transfecting Glioma Cells Mediated by Neurokinin-1 Receptor

Author(s):  
Guihua Ding ◽  
Taoran Wang ◽  
Zhenbin Han ◽  
Long Tian ◽  
Qin Cheng ◽  
...  

Gene therapy provides a promising treatment for glioblastoma multiforme, which mainly depends on two keys, crossing the blood brain barrier (BBB) effectively and transfecting target cells selectively. In this work,...

2021 ◽  
Author(s):  
Moataz Dowaidar

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.


2020 ◽  
Vol 6 (12) ◽  
pp. 6778-6789
Author(s):  
Taoran Wang ◽  
Zhao Meng ◽  
Ziyao Kang ◽  
Guihua Ding ◽  
Baoquan Zhao ◽  
...  

2015 ◽  
Vol 7 (2) ◽  
Author(s):  
Stephen Patrick Loughran ◽  
Cian Michael McCrudden ◽  
Helen Olga McCarthy

AbstractGene therapy has long been hailed as a revolutionary approach for the treatment of genetic diseases. The enthusiasm that greeted the harnessing of viruses for therapeutic DNA delivery has been tempered by concerns over safety. These concerns led to the development of alternative strategies for nucleic acid delivery to cells. One such strategy is the utilization of cationic peptides for the condensation of therapeutic DNA for delivery to its target. However, success of DNA as a therapy relies on its delivery to the nucleus of target cells, a process that is complicated by the many hurdles encountered following systemic administration. Non-viral peptide gene delivery strategies have sought inspiration from viruses in order to retain DNA delivering potency, but limit virulence. This review summarizes the progression of peptide-based DNA delivery systems, from rudimentary beginnings to the recent development of sophisticated multi-functional vectors that comprise distinct motifs with dedicated barrier evasion functions. The most promising peptides that achieve cell membrane permeabilization, endosomal escape and nuclear delivery are discussed.


2021 ◽  
Vol 11 ◽  
Author(s):  
Junsheng Li ◽  
Wen Wang ◽  
Jia Wang ◽  
Yong Cao ◽  
Shuo Wang ◽  
...  

Glioblastoma multiforme (GBM), as one of the most common malignant brain tumors, was limited in its treatment effectiveness with current options. Its invasive and infiltrative features led to tumor recurrence and poor prognosis. Effective treatment and survival improvement have always been a challenge. With the exploration of genetic mutations and molecular pathways in neuro-oncology, gene therapy is becoming a promising therapeutic approach. Therapeutic genes are delivered into target cells with viral vectors to act specific antitumor effects, which can be used in gene delivery, play an oncolysis effect, and induce host immune response. The application of engineering technology makes the virus vector used in genetics a more prospective future. Recent advances in viral gene therapy offer hope for treating brain tumors. In this review, we discuss the types and designs of viruses as well as their study progress and potential applications in the treatment of GBM. Although still under research, viral gene therapy is promising to be a new therapeutic approach for GBM treatment in the future.


2019 ◽  
Vol 7 (11) ◽  
pp. 1824-1841 ◽  
Author(s):  
Ziyao Kang ◽  
Qingbin Meng ◽  
Keliang Liu

Gene therapy as a strategy for disease treatment requires safe and efficient gene delivery systems that encapsulate nucleic acids and deliver them to effective sites in the cell.


2021 ◽  
Author(s):  
Moataz Dowaidar

Gene therapy was first established in 1972, and since then, it has made great progress in terms of adoption. The efficiency of the gene transfer carrier is critical to the success of gene therapy. As a result, researchers are always looking for a secure, specialized, and efficient mode of transportation. In recent years, the newly discovered exosomal transport mechanism has made significant progress. Viruses, bacteria, phages, and synthetic lipids-based delivery methods are less stable, biocompatible, and can cross the blood-brain barrier. The majority of the research has focused on creating exosomes that transport therapeutic miRNA to specific target cells. Despite the excellent results, there are still some concerns about employing exosomes as a gene therapy carrier. The miRNA mechanism is becoming increasingly apparent for a specific condition, yet one miRNA can influence several genes. Furthermore, nothing is known about numerous non-disease related gene interactions. Although high levels of certain exocrine miRNA may aid in the treatment of some disorders, nothing is known about potential side effects. Exosomes still need to be researched and manufactured more efficiently. While exosomes have significant promise for gene therapy, using exocrine miRNAs to treat disorders is difficult and requires further research and development by academics and clinicians.


2018 ◽  
Vol 9 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Aparna Bansal ◽  
Himanshu

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.


2019 ◽  
Vol 12 (1) ◽  
pp. 84-90 ◽  
Author(s):  
Nobuhiko Seki ◽  
Ryosuke Ochiai ◽  
Terunobu Haruyama ◽  
Masashi Ishihara ◽  
Maika Natsume ◽  
...  

Common dermatological side-effects associated with erlotinib, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), include pruritus and skin rash, which are mediated by substance P, leading to the occasional discontinuation of cancer treatment. Aprepitant is an antagonist of neurokinin-1 receptor, through which substance P activates the pruritogens. Thus, aprepitant is expected to offer a promising option for the treatment of erlotinib-induced pruritus. However, the appropriate treatment schedule for aprepitant administration is under consideration. Here, we discuss the need for flexible adjustment of the treatment schedule for aprepitant administration against erlotinib-induced refractory pruritus and skin rush. A 71-year-old female smoker presented with stage IV EGFR-mutated lung adenocarcinoma. She was started on erlotinib at 150 mg/day. However, by 28 days, severe pruritus and acneiform skin rush resistant to standard therapies occurred, resulting in the interruption of erlotinib therapy. After recovery, she was restarted on erlotinib at 100 mg/day. However, severe pruritus and skin rush developed again within 2 weeks. Then, we started the first 3-day dose of aprepitant (125 mg on day 1, 80 mg on day 3, and 80 mg on day 5) based on the results of the previous prospective study, which showed the success rate of 100% with at least the second dose of aprepitant. However, the pruritus and skin rush exacerbated again within 4 weeks. Therefore, we started the second 3-day dose of aprepitant, but in vain. At this point, as the patient-centered medicine, bi-weekly schedule of the 3-day dose of aprepitant was considered and, then, adopted. As the results, the pruritus and skin rush remained well-controlled throughout the subsequent treatment with erlotinib.


Author(s):  
Yongtao Wang ◽  
Yingjun Yang ◽  
Toru Yoshitomi ◽  
Naoki Kawazoe ◽  
Yingnan Yang ◽  
...  

Gene transfection has been widely studied due to its potential applications in tissue repair and gene therapy. Many studies have focused on designing gene carriers and developing novel transfection techniques....


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