Hepatoma-targeted gene delivery using a tumor cell–specific gene regulation system combined with a human liver cell–specific bionanocapsule

Kang, Jeong Hun; Oishi, Jun; Kim, Jong Hwan; Ijuin, Moeko; Toita, Riki; Jun, Byungdug; Asai, Daisuke; Mori, Takeshi; Niidome, Takuro; Tanizawa, Katsuyuki; Kuroda, Shinya; Katayama, Yoshiki

doi:10.1016/j.nano.2010.01.007

Cited by 22 publications

(20 citation statements)

References 25 publications

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“…[1][2][3][4] Conventional chemotherapeutic agents diffuse nonspecifically throughout the body where they affect both malignant and normal cells; unfortunately, 95% of all new potential therapeutics have poor pharmacokinetic and biopharmaceutical properties. 5 To overcome these problems, there is a serious need to develop effective drug delivery systems (DDS) that distribute therapeutically active drug molecules only to the desired site of action without affecting healthy organs and tissues.…”

Section: Introductionmentioning

confidence: 99%

Liver cell specific targeting by the preS1 domain of hepatitis B virus surface antigen displayed on protein nanocages

Murata¹,

Narahara²,

Umezaki³

et al. 2012

IJN

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Abstract:Protein nanocages are self-organized complexes of oligomers whose three-dimensional architecture can been determined in detail. These structures possess nanoscale inner cavities into which a variety of molecules, including therapeutic or diagnostic agents, can be encapsulated. These properties yield these particles suitable for a new class of drug delivery carrier, or as a bioimaging reagent that might respond to biochemical signals in many different cellular processes. We report here the design, synthesis, and biological characterization of a hepatocyte-specific nanocage carrying small heat-shock protein. These nanoscale protein cages, with a targeting peptide composed of a preS1 derivative from the hepatitis B virus on their surfaces, were prepared by genetic engineering techniques. PreS1-carrying nanocages showed lower cytotoxicity and significantly higher specificity for human hepatocyte cell lines than other cell lines in vitro. These results suggested that small heat-shock protein-based nanocages present great potential for the development of effective targeted delivery of various agents to specific cells.

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Section: Introductionmentioning

confidence: 99%

Liver cell specific targeting by the preS1 domain of hepatitis B virus surface antigen displayed on protein nanocages

Murata¹,

Narahara²,

Umezaki³

et al. 2012

IJN

Self Cite

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“…Most research efforts to secure the cell specificity have focused on an active targeting strategy using specific interaction between cellular surface marker molecules and their specific ligands introduced into the gene carrier. Our group has developed gene delivery systems recognizing cell receptors [3] or responding to hyperactivated cellular signals [4]. Recently, we synthesized a polyethylenimine (PEI)-pullulan carrier as a promising system for liver-targeted gene delivery.…”

Section: S6-mentioning

confidence: 99%

“…A mouse model of PKU (Pah enu2 strain with a missense mutation in the PAH gene) has been used to explore the gene therapy strategies. A straightforward approach is to transfer a functional PAH gene to the liver, where Phe is metabolized with the endogenous BH 4 . So far we and other investigators have successfully corrected HPA in Pah enu2 mice with adeno-associated virus (AAV) vectors, most recently pseudotyped with AAV8 capsid.…”

Section: S8-2 Gene Therapy For Phenylketonuriamentioning

confidence: 99%

“…Cancer Center, Nagoya, Aichi, Japan. 4 Department of Immuno-Genet Therapy, Mie University, Tsu, Japan.…”

Section: Aimmentioning

confidence: 99%

“…Among them, sonoporation method would be a promising approach for efficient targeted gene delivery because combination of ligand modified liposomal bubble and ultrasound exposure method enable to obtain the efficient-and cell-selective gene transfer at targeted site. We have been developed glycosylated liposomes for cell-selective and efficient delivery of nucleic acids via receptor-mediated endocytosis [1][2][3][4]. Recently, we succeeded to develop an ultrasound-mediated transfection method using Man-PEG 2000 bubble lipoplexes, which are ultrasound-responsive and mannose-modified gene carriers to obtain the efficient gene transfer into mannose receptor-expressing cells selectively [5].…”

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The 17th Annual Meeting 2011 Japan Society of Gene Therapy

2014

The Journal of Gene Medicine

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Cancer treatment has been improved by recent progress in multimodal treatments. However, only palliative therapies remain for patients who have disease that is refractory to standard therapies including surgery, chemotherapy, or radiotherapy. The development of novel therapies is an urgent social need for such refractory cases. Gene therapy has been considered to be one of the so-called fourth therapies for cancer treatment. Although several approaches have shown some benefit, their clinical efficacies have generally been insufficient and unpredictable. The development of a new strategy to induce and maintain antitumor effects for longer periods in predictable way is imminent. To establish a new generation of antitumor therapies, we conducted several phase I clinical studies of immune and cell therapies targeting metastatic solid tumors. Our first phase I study involved immune gene therapy using a GM-CSF gene-transduced autologous tumor vaccine for stage IV renal cell cancer. Our results showed that this new immune gene therapy was safe and induced tumor-specific immune reactions in patients. Two out of four patients survived for more than six years. However, the clinical antitumor effect, i.e., reducing the size of large tumor masses, was inadequate with this approach alone. To overcome this limitation, we next used a mouse tumor model to explore several combination therapies for enhancing GM-CSF gene therapy. Our results demonstrated the effectiveness of the combined use of the TARC and RANTES chemokine genes with the GM-CSF gene. In the clinical setting, we adopted new cell therapy methods, using tumor associated antigen (TAA)pulsed dendritic cells with cytotoxic T cells, involving the breakage of immune tolerance and the induction of TAA-specific immune responses. This phase I clinical trial is now underway and thus far no severe adverse events have been observed. The combination of GM-CSF gene therapy followed by novel immune cell therapy may be our next challenge. Our second gene therapy approach is oncolytic virotherapy, with current targets of measles virus and enterovirus. Our mouse tumor model studies demonstrated that both viruses would be promising candidates. Collectively, we hope that both immune gene therapy and virotherapy will cast a new light on the field of clinical cancer treatment in near future.Special Lecture I Viruses as Allies of Man: From Swords to PloughsharesInder Verma Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037-1002, USA At the beginning of the third millennium, man has an opportunity to fulfill the cherished goal of improving the lot of humankind. Newer modalities of medicine are being practiced and daily new breakthroughs are being reported. I would like to talk about gene therapy, a form of molecular medicine, which will have a major impact on human health. At present, gene therapy is being contemplated for both genetic and acquired diseases. These include hemophilia, cystic fibrosis, diabetes, canc...

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Hepatitis B virus pre‐S region: Clinical implications and applications

Sun

Chang

Yan

et al. 2020

Reviews in Medical Virology

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Hepatitis B virus (HBV) infection is a major threat to global public health, which can result in many acute and chronic liver diseases. HBV, a member of the family Hepadnaviridae, is a small enveloped DNA virus containing a circular genome of 3.2 kb. Located upstream of the S-open-reading frame of the HBV genome is the pre-S region, which is vital to the viral life cycle. The pre-S region has high variability and many mutations in the pre-S region are associated with several liver diseases, such as fulminant hepatitis (FH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). In addition, the pre-S region has been applied in the development of several pre-S-based materials and systems to prevent or treat HBV infection. In conclusion, the pre-S region plays an essential role in the occurrence, diagnosis, and treatment of HBV-related liver diseases, which may provide a novel perspective for the study of HBV infection and relevant diseases. K E Y W O R D Shepatitis B virus (HBV), pre-S mutants, occult HBV infection | INTRODUCTIONHepatitis B is a non-negligible, life-threatening liver infection caused by the hepatitis B virus (HBV). It can progress to chronic infection, putting infected people at enormous risk of developing liver cirrhosis (LC), hepatocellular carcinoma (HCC), and even causing death. 1 A total of 257 million people worldwide have been chronically infected with HBV as of 2016, and it results in an estimated 887,000 deaths annually. 2 Hepatitis B has imposed huge burdens on many countries, and it remains a global public health problem that requires an urgent response.HBV belongs to the family Hepadnaviridae and is a small enveloped DNA virus. The viral genome is a partially double-stranded DNA with approximately 3200 base pairs. Based on the sequence divergence of the full HBV genome, 10 genotypes (A to J) and several subtypes of HBV have been identified, with different geographical distributions. 3 Four partially overlapping open-reading frames (ORFs) in the viral genome (pre-S/S, pre-C/C, P, and X) are responsible for encoding essential proteins for the viral life cycle. Among them, the pre-S/S ORF encodes three enveloped/surface proteins, that is, Large (L), Middle (M), and Small (S) proteins. 4 In fact, in addition to encoding surface proteins, the pre-S domain is reported to have many other important functions in the HBV life cycle, such as mediating HBV infection, forming viral particles, and inducing host immune responses. 5 The pre-S region has high variability, and mutations of the pre-S region have been confirmed to be related to several different acute and chronic liver diseases, which are of great clinical significance. 6 Moreover, the pre-S domain has displayed good

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Hepatoma-targeted gene delivery using a tumor cell–specific gene regulation system combined with a human liver cell–specific bionanocapsule

Cited by 22 publications

References 25 publications

Liver cell specific targeting by the preS1 domain of hepatitis B virus surface antigen displayed on protein nanocages

Liver cell specific targeting by the preS1 domain of hepatitis B virus surface antigen displayed on protein nanocages

The 17th Annual Meeting 2011 Japan Society of Gene Therapy

Hepatitis B virus pre‐S region: Clinical implications and applications

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