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Cancers
Special Issues
Gene Editing and Delivery for Cancer Therapy
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Gene Editing and Delivery for Cancer Therapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (5 July 2023) | Viewed by 9874

Special Issue Editors

Dr. Yong Teng

E-Mail Website
Guest Editor
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA
Interests: metastasis; molecular pathway; cancer models; metabolism; tumor microenvironment; drug screening and development
Special Issues, Collections and Topics in MDPI journals
Dr. Yamin Li

E-Mail Website
Guest Editor
Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA
Interests: drug delivery; lipid nanoparticles; gene editing; nanomedicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Cancer is a leading cause of human death worldwide. An estimated 19.3 million cancer incidents and 10.0 million cancer deaths occurred in 2020. Due to the population growth and aging, it is expected that there will be 27.5 million new cancer cases and 16.3 million cancer deaths by 2040. Gene therapy has potential in the treatment of human cancers. However, it has only achieved little success in clinical practice due to a lack of efficient in vivo gene editing and delivery systems. Therefore, revolutionizing new technologies in gene editing and engineering gene delivery systems that specifically target the neoplastic tissue are critical to overcoming current limitations in gene therapy. For this purpose, biodegradable lipid, polymer, and inorganic nanomaterials have been extensively explored as delivery vehicles for siRNA, mRNA, antisense oligonucleotides, CRISPR/Cas9, and more, holding great promises in improving gene silencing and genome editing in cancer tissues. Other such tools include oncolytic viruses, DNA/RNA nanostructures, therapeutic peptides and exosomes. Despite the tremendous advancements, gene therapy remains multiple obstacles before successful clinical translation, including its efficacy and safety profiles and the escalating manufacturing complexity. Accordingly, this Special Issue seeks research papers, short communications, and review articles that focus on novel design and applications of gene editing and delivery that can overcome one or several significant barriers limiting the successful translation of gene therapy in cancer treatment.

Dr. Yong Teng
Dr. Yamin Li
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gene therapy
  • gene editing
  • gene delivery
  • oncolytic viruses
  • nanomaterial
  • peptides
  • nanostructures
  • exosomes
  • translational science

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Published Papers (3 papers)

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Research

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16 pages, 8881 KiB  
Article
Early Subcellular Hepatocellular Alterations in Mice Post Hydrodynamic Transfection: An Explorative Study
by Mohd Yasser, Silvia Ribback, Katja Evert, Kirsten Utpatel, Katharina Annweiler, Matthias Evert, Frank Dombrowski and Diego F. Calvisi
Cancers 2023, 15(2), 328; https://doi.org/10.3390/cancers15020328 - 4 Jan 2023
Viewed by 3277
Abstract
Hydrodynamic transfection (HT) or hydrodynamic tail vein injection (HTVi) is among the leading technique that is used to deliver plasmid genes mainly into the liver of live mice or rats. The DNA constructs are composed of coupled plasmids, while one contains the gene [...] Read more.
Hydrodynamic transfection (HT) or hydrodynamic tail vein injection (HTVi) is among the leading technique that is used to deliver plasmid genes mainly into the liver of live mice or rats. The DNA constructs are composed of coupled plasmids, while one contains the gene of interest that stably integrate into the hepatocyte genome with help of the other consisting sleeping beauty transposase system. The rapid injection of a large volume of DNA-solution through the tail vein induces an acute cardiac congestion that refluxed into the liver, mainly in acinus zone 3, also found through our EM study. Although, HT mediated hydrodynamic force can permeabilizes the fenestrated sinusoidal endothelium of liver, but the mechanism of plasmid incorporation into the hepatocytes remains unclear. Therefore, in the present study, we have hydrodynamically injected 2 mL volume of empty plasmid (transposon vector) or saline solution (control) into the tail vein of anesthetized C57BL/6J/129Sv mice. Liver tissue was resected at different time points from two animal group conditions, i.e., one time point per animal (1, 5, 10–20, 60 min or 24 and 48 hrs after HT) or multiple time points per animal (0, 1, 2, 5, 10, 20 min) and quickly fixed with buffered 4% osmium tetroxide. The tissues fed with only saline solution was also resected and fixed in the similar way. EM evaluation from the liver ultrathin sections reveals that swiftly after 1 min, the hepatocytes near to the central venule in the acinus zone 3 shows cytoplasmic membrane-bound vesicles. Such vesicles increased in both numbers and size to vacuoles and precisely often found in the proximity to the nucleus. Further, EM affirm these vacuoles are also optically empty and do not contain any electron dense material. Although, some of the other hepatocytes reveals sign of cell damage including swollen mitochondria, dilated endoplasmic reticulum, Golgi apparatus and disrupted plasma membrane, but most of the hepatocytes appeared normal. The ultrastructural findings in the mice injected with empty vector or saline injected control mice were similar. Therefore, we have interpreted the vacuole formation as nonspecific endocytosis without specific interactions at the plasma membrane. Full article
(This article belongs to the Special Issue Gene Editing and Delivery for Cancer Therapy)
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17 pages, 2711 KiB  
Article
Retroviral Replicating Vector Toca 511 (Vocimagene Amiretrorepvec) for Prodrug Activator Gene Therapy of Lung Cancer
by Hiroki Kushiya, Kei Hiraoka, Tomohiro Suzuki, Kazuho Inoko, Akihito Inagaki, Hiroki Niwa, Katsunori Sasaki, Toru Nakamura, Takahiro Tsuchikawa, Toshiaki Shichinohe, Douglas J. Jolly, Noriyuki Kasahara and Satoshi Hirano
Cancers 2022, 14(23), 5820; https://doi.org/10.3390/cancers14235820 - 25 Nov 2022
Cited by 8 | Viewed by 1756
Abstract
Therapeutic efficacy of retroviral replicating vector (RRV)-mediated prodrug activator gene therapy has been demonstrated in a variety of tumor models, but clinical investigation of this approach has so far been restricted to glioma and gastrointestinal malignancies. In the present study, we evaluated replication [...] Read more.
Therapeutic efficacy of retroviral replicating vector (RRV)-mediated prodrug activator gene therapy has been demonstrated in a variety of tumor models, but clinical investigation of this approach has so far been restricted to glioma and gastrointestinal malignancies. In the present study, we evaluated replication kinetics, transduction efficiency, and therapeutic efficacy of RRV in experimental models of lung cancer. RRV delivering GFP as a reporter gene showed rapid viral replication in a panel of lung cancer cells in vitro, as well as robust intratumoral replication and high levels of tumor transduction in subcutaneous and orthotopic pleural dissemination models of lung cancer in vivo. Toca 511 (vocimagene amiretrorepvec), a clinical-stage RRV encoding optimized yeast cytosine deaminase (yCD) which converts the prodrug 5-fluorocytosine (5-FC) to the active drug 5-fluorouracil (5-FU), showed potent cytotoxicity in lung cancer cells upon exposure to 5-FC prodrug. In vivo, Toca 511 achieved significant tumor growth inhibition following 5-FC treatment in subcutaneous and orthotopic pleural dissemination models of lung cancer in both immunodeficient and immunocompetent hosts, resulting in significantly increased overall survival. This study demonstrates that RRV can serve as highly efficient vehicles for gene delivery to lung cancer, and indicates the translational potential of RRV-mediated prodrug activator gene therapy with Toca 511/5-FC as a novel therapeutic strategy for pulmonary malignancies. Full article
(This article belongs to the Special Issue Gene Editing and Delivery for Cancer Therapy)
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Review

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17 pages, 512 KiB  
Review
Cell-Penetrating Peptides (CPPs) as Therapeutic and Diagnostic Agents for Cancer
by Ryan A. Bottens and Tohru Yamada
Cancers 2022, 14(22), 5546; https://doi.org/10.3390/cancers14225546 - 11 Nov 2022
Cited by 23 | Viewed by 4036
Abstract
Cell-Penetrating Peptides (CPPs) are short peptides consisting of <30 amino acids. Their ability to translocate through the cell membrane while carrying large cargo biomolecules has been the topic of pre-clinical and clinical trials. The ability to deliver cargo complexes through membranes yields potential [...] Read more.
Cell-Penetrating Peptides (CPPs) are short peptides consisting of <30 amino acids. Their ability to translocate through the cell membrane while carrying large cargo biomolecules has been the topic of pre-clinical and clinical trials. The ability to deliver cargo complexes through membranes yields potential for therapeutics and diagnostics for diseases such as cancer. Upon cellular entry, some CPPs have the ability to target specific organelles. CPP-based intracellular targeting strategies hold tremendous potential as they can improve efficacy and reduce toxicities and side effects. Further, recent clinical trials show a significant potential for future CPP-based cancer treatment. In this review, we summarize recent advances in CPPs based on systematic searches in PubMed, Embase, Web of Science, and Scopus databases until 30 September 2022. We highlight targeted delivery and explore the potential uses for CPPs as diagnostics, drug delivery, and intrinsic anti-cancer agents. Full article
(This article belongs to the Special Issue Gene Editing and Delivery for Cancer Therapy)
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