Advances in delivery vectors for gene therapy in liver cancer

2020 ◽  
Vol 11 (1) ◽  
pp. 833-850 ◽  
Author(s):  
Katherine E Redd Bowman ◽  
Phong Lu ◽  
Erica R Vander Mause ◽  
Carol S Lim
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gene Therapy ◽  
Viral Vectors ◽  
Gene Editing ◽  
Cancer Death ◽  
Common Cause ◽  
The Third ◽  
Gene Delivery Vectors ◽  
Efficient Delivery ◽  
Therapy Delivery

Hepatocellular carcinoma (HCC) is the third most common cause of cancer death globally, mainly due to lack of effective treatments – a problem that gene therapy is poised to solve. Successful gene therapy requires safe and efficient delivery vectors, and recent advances in both viral and nonviral vectors have made an important impact on HCC gene therapy delivery. This review explores how adenoviral, retroviral and adeno-associated viral vectors have been modified to increase safety and delivery capacity, highlighting studies and clinical trials using these vectors for HCC gene therapy. Nanoparticles, liposomes, exosomes and virosomes are also featured in their roles as HCC gene delivery vectors. Finally, new discoveries in gene editing technology and their impacts on HCC gene therapy are discussed.

scholarly journals Abdominal Ultrasound and Treatment of Hepatocellular Carcinoma

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1268
Author(s):  
Kazushi Numata
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Abdominal Ultrasound ◽  
Cancer Death ◽  
Common Cause ◽  
Cancer Statistics ◽  
The Third ◽  
Common Cancer

Liver cancer is the sixth most common cancer and the third most common cause of cancer death, based on Global Cancer Statistics 2020 [...]

scholarly journals Intratracheal aerosolization of viral vectors to newborn pig airways

BioTechniques ◽  
2020 ◽  
Vol 68 (5) ◽  
pp. 235-239
Author(s):  
Ashley L Cooney ◽  
Patrick L Sinn
Keyword(s):  
Gene Therapy ◽  
Animal Models ◽  
Endotracheal Tube ◽  
Viral Vectors ◽  
Small Animal ◽  
Large Animal ◽  
Large Animal Models ◽  
Airway Diseases ◽  
Efficient Delivery ◽  
Large Animals

Gene therapy for airway diseases requires efficient delivery of nucleic acids to the airways. In small animal models, gene delivery reagents are commonly delivered as a bolus dose. However, large animal models are often more relevant for the transition from preclinical studies to human trials. Aerosolizing viral vectors to the lungs of large animals can maximize anatomical distribution. Here, we describe a technique for aerosolization of viral vectors to the airways of newborn pigs. Briefly, a pig is anesthetized and intubated with an endotracheal tube, and a microsprayer is passed through the endotracheal tube. A fine mist is then sprayed into the distal trachea. Widespread and uniform distribution of transgene expression is critical for developing successful lung gene therapy treatments.

scholarly journals An Overview of Bacterial and Viral Inhibitors Involved in Gene Therapy of Hepatocellular Carcinoma (Hcc)

2021 ◽  
Vol 6 (3) ◽  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gene Therapy ◽  
Viral Vectors ◽  
Viral Infections ◽  
Bacterial Species ◽  
Molecular Alterations ◽  
Experimental Approaches ◽  
Bacteria And Fungi ◽  
Insight Into ◽  
Viral Inhibitors

Hepatocellular carcinoma (HCC) is a form of cancer that is very widespread around the world and has a high mortality rate. Extensive evidence suggests that, HCC is a multifactorial disease. Hepatic cirrhosis is present, along with systemic inflammation and viral infections such as hepatitis B or C. Thus, giving rise to genetically and phenotypically heterogeneous hepatocellular carcinoma tumors. Researchers have found that bacterial and viral inhibitors can be used to silence targeted genes in hepatocellular carcinoma. Many bacterial species such as; Salmonella, Listeria, and Escherichia, proved to have anti-tumor properties. Up till now, adenoviral, retroviral, herpes-simplex viral and adeno-associated viral vectors have been modified and are being used for HCC gene therapy. In patients, up regulation of TLR signaling have also been observed showing an interesting influence on HCC’s microenvironment. TLR 4 and TLR 9 have positive relationship with tumor whereas, TLR3 is associated with anti-tumor influence. TLRs can cause an inflammatory response in the presence of foreign pathogens including bacteria and fungi. This review reflects an insight into the biology of HCC suggesting that certain signaling pathways and molecular alterations plays a very significant role in HCC development. As well as new experimental approaches, including; anti-angiogenesis, cancer therapy, oncolytic virotherapy, and suppressing the function of oncogenes, leading to apoptosis are successively being applied. The current challenge for the researchers is to identify a medicament which is selective for tumors specific cells only, having minimal noxiousness and harmless to normal tissue. We have scrutinized research articles based on how to merge viral and bacterial anticancer therapies into a single treatment for HCC.

Troxerutin subdues hepatic tumorigenesis via disrupting the MDM2–p53 interaction

2018 ◽  
Vol 9 (10) ◽  
pp. 5336-5349 ◽  
Author(s):  
Nisha Susan Thomas ◽  
Kiran George ◽  
Athavan Alias Anand Selvam
Keyword(s):  
Hepatocellular Carcinoma ◽  
Common Cause ◽  
The Third ◽  
Common Cancer ◽  
Hepatic Tumorigenesis

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most common cause of mortality worldwide.

Xyloglucan as a mitomycin C carrier to reverse multidrug resistance

RSC Advances ◽  
2016 ◽  
Vol 6 (109) ◽  
pp. 107800-107809 ◽  
Author(s):  
Chang Wang ◽  
Jean Felix Mukerabigwi ◽  
Shiying Luo ◽  
Yuannian Zhang ◽  
Xuan Xie ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Developing Countries ◽  
Multidrug Resistance ◽  
Mitomycin C ◽  
Cancer Death ◽  
The Third

Hepatocellular carcinoma (HCC) is still considered as the third highest cause of cancer death in developing countries.

scholarly journals Assessment of Current Gene Therapy Practices in Hepatocellular Carcinoma

2020 ◽  
Vol 2 (4) ◽  
pp. 469-480
Author(s):  
Bryan Mckiver ◽  
Mohamad Imad Damaj ◽  
Devanand Sarkar
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gene Therapy ◽  
Late Stage ◽  
Viral Vectors ◽  
Primary Liver Cancer ◽  
Treatment Options ◽  
Diagnostic Tools ◽  
In Vivo Models

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and the fifth most common cancer worldwide. HCC is recognized as the fourth most common cause of cancer related deaths worldwide due to the lack of effective early diagnostic tools, which often leads to individuals going undiagnosed until the cancer has reached late stage development. The current FDA approved treatments for late stage HCC provide a minimal increase in patient survival and lack tumor specificity, resulting in toxic systemic side effects. Gene therapy techniques, such as chimeric antigen receptor (CAR)-T Cells, viral vectors, and nanoparticles, are being explored as novel treatment options in various genetic diseases. Pre-clinical studies using gene therapy to treat in vitro and in vivo models of HCC have demonstrated potential efficacy for use in human patients. This review highlights genetic targets, techniques, and current clinical trials in HCC utilizing gene therapy.

scholarly journals Gene Therapy in Rare Respiratory Diseases: What Have We Learned So Far?

2020 ◽  
Vol 9 (8) ◽  
pp. 2577 ◽  
Author(s):  
Lucía Bañuls ◽  
Daniel Pellicer ◽  
Silvia Castillo ◽  
María Mercedes Navarro-García ◽  
María Magallón ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Respiratory Diseases ◽  
Viral Vectors ◽  
Gene Editing ◽  
Alternative Therapy ◽  
Transcription Activator ◽  
Gene Therapy Approach ◽  
Gene Therapy Application ◽  
Alpha 1 Antitrypsin Deficiency

Gene therapy is an alternative therapy in many respiratory diseases with genetic origin and currently without curative treatment. After five decades of progress, many different vectors and gene editing tools for genetic engineering are now available. However, we are still a long way from achieving a safe and efficient approach to gene therapy application in clinical practice. Here, we review three of the most common rare respiratory conditions—cystic fibrosis (CF), alpha-1 antitrypsin deficiency (AATD), and primary ciliary dyskinesia (PCD)—alongside attempts to develop genetic treatment for these diseases. Since the 1990s, gene augmentation therapy has been applied in multiple clinical trials targeting CF and AATD, especially using adeno-associated viral vectors, resulting in a good safety profile but with low efficacy in protein expression. Other strategies, such as non-viral vectors and more recently gene editing tools, have also been used to address these diseases in pre-clinical studies. The first gene therapy approach in PCD was in 2009 when a lentiviral transduction was performed to restore gene expression in vitro; since then, transcription activator-like effector nucleases (TALEN) technology has also been applied in primary cell culture. Gene therapy is an encouraging alternative treatment for these respiratory diseases; however, more research is needed to ensure treatment safety and efficacy.

Extended Abstract: Management of Liver Cancer

2016 ◽  
Vol 34 (4) ◽  
pp. 438-439 ◽  
Author(s):  
Peter Robert Galle
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Associated Factors ◽  
Progressive Disease ◽  
Patient Survival ◽  
Western World ◽  
Tumor Treatment ◽  
Common Cause ◽  
The Third ◽  
Liver Cancers

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. HCC represents more than 90% of primary liver cancers. There is a growing incidence of HCC worldwide. In the Western world, HCC arises in a cirrhotic background in up to 90% of cases, and cirrhosis itself is a progressive disease that affects patient survival. Thus, outcome in patients with HCC and the chances for anti-tumor treatment and its results are dependent not only on tumor-associated factors but also on liver function.

scholarly journals Potential of helper-dependent Adenoviral vectors in CRISPR-cas9-mediated lung gene therapy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ranmal Avinash Bandara ◽  
Ziyan Rachel Chen ◽  
Jim Hu
Keyword(s):  
Cystic Fibrosis ◽  
Gene Therapy ◽  
Lung Disease ◽  
Viral Vectors ◽  
Gene Editing ◽  
Genetic Diseases ◽  
Adenoviral Vectors ◽  
The Status

AbstractSince CRISPR/Cas9 was harnessed to edit DNA, the field of gene therapy has witnessed great advances in gene editing. New avenues were created for the treatment of diseases such as Cystic Fibrosis (CF). CF is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Despite the success of gene editing with the CRISPR/Cas9 in vitro, challenges still exist when using CRISPR/Cas9 in vivo to cure CF lung disease. The delivery of CRISPR/Cas9 into lungs, as well as the difficulty to achieve the efficiency required for clinical efficacy, has brought forth new challenges. Viral and non-viral vectors have been shown to deliver DNA successfully in vivo, but the sustained expression of CFTR was not adequate. Before the introduction of Helper-Dependent Adenoviral vectors (HD-Ad), clinical trials of treating pulmonary genetic diseases with first-generation viral vectors have shown limited efficacy. With the advantages of larger capacity and lower immunogenicity of HD-Ad, together with the versatility of the CRISPR/Cas9 system, delivering CRISPR/Cas9 to the airway with HD-Ad for lung gene therapy shows great potential. In this review, we discuss the status of the application of CRISPR/Cas9 in CF gene therapy, the existing challenges in the field, as well as new hurdles introduced by the presence of CRISPR/Cas9 in the lungs. Through the analysis of these challenges, we present the potential of CRISPR/Cas9-mediated lung gene therapy using HD-Ad vectors with Cystic Fibrosis lung disease as a model of therapy.

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