scholarly journals Characterization of iRGD-Ligand Modified Arginine-Histidine-Rich Peptides for Nucleic Acid Therapeutics Delivery to αvβ3 Integrin-Expressing Cancer Cells

2020 ◽  
Vol 13 (10) ◽  
pp. 300
Author(s):  
Anna Egorova ◽  
Alexander Selutin ◽  
Marianna Maretina ◽  
Sergei Selkov ◽  
Vladislav Baranov ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Nucleic Acid ◽  
Cancer Cells ◽  
Transfection Efficiency ◽  
Cancer Gene Therapy ◽  
Αvβ3 Integrin ◽  
Cancer Gene ◽  
Kinase Gene ◽  
Peptide Carrier ◽  
Αvβ3 Integrins

Efficient and specific delivery of nucleic acid (NA) therapeutics to tumor cells is extremely important for cancer gene therapy. Various therapeutic strategies include delivery of DNA-therapeutics such as immunostimulatory or suicide genes and delivery of siRNA-therapeutics able to silence expression of cancer-related genes. Peptides are a promising class of non-viral vehicles which are biodegradable and can efficiently condense, protect and specifically deliver NA to the cells. Here we designed arginine-histidine-rich peptide carriers consisting of an iRGD ligand to target αvβ3 integrins and studied them as vehicles for DNA and siRNA delivery to cancer cells. Combination of iRGD-modified and unmodified arginine–histidine-rich peptides during NA complexation resulted in carriers with different ligand contents. The NA-binding and protecting properties in vitro transfection efficiency and cytotoxicity of the DNA- and siRNA-polyplexes were studied and the most efficient carrier RGD1 was determined. The ability of the peptides to mediate specific intracellular uptake was confirmed inhuman cervical carcinoma (HeLa), human kidney (293T) and human pancreatic (PANC-1) cell lines with different αvβ3 integrins surface expression. By means of RGD1 carrier, efficient delivery of the herpes simplex virus (HSV-1) thymidine kinase gene to PANC-1 cells was demonstrated. Subsequent ganciclovir treatment led to a reduction of PANC-1 cells’ viability by up to 54%. Efficient RNAi-mediated down-regulation of GFP and VEGFA gene expression was achieved in MDA-MB-231-GFP+ breast cancer and EA.hy926 endothelial cells, respectively, by means of RGD1/siRNA polyplexes. Here we demonstrated that the peptide carrier RGD1 can be considered as promising candidate for development of NA therapeutics delivery systems useful in cancer gene therapy.

scholarly journals Development of iRGD-Modified Peptide Carriers for Suicide Gene Therapy of Uterine Leiomyoma

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 202
Author(s):  
Anna Egorova ◽  
Sofia Shtykalova ◽  
Alexander Selutin ◽  
Natalia Shved ◽  
Marianna Maretina ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Uterine Leiomyoma ◽  
Transfection Efficiency ◽  
Chemical Properties ◽  
Suicide Gene ◽  
Suicide Gene Therapy ◽  
Benign Tumors ◽  
Αvβ3 Integrin ◽  
Peptide Carrier ◽  
Plasmid Delivery

Uterine leiomyoma (UL) is one of the most common benign tumors in women that often leads to many reproductive complications. Suicide genetherapy was suggested as a promising approach for UL treatment. In the present study, we describe iRGD ligand-conjugated cysteine-rich peptide carrier RGD1-R6 for targeted DNA delivery to αvβ3 integrin-expressing primary UL cells. The physico-chemical properties, cytotoxicity, transfection efficiency and specificity of DNA/RGD1-R6 polyplexes were investigated. TheHSV-1thymidine kinase encoding plasmid delivery to PANC-1pancreatic carcinoma cells and primary UL cells resulted in significant suicide gene therapy effects. Subsequent ganciclovir treatment decreased cells proliferative activity, induced of apoptosis and promoted cells death.The obtained results allow us to concludethatthe developed RGD1-R6 carrier can be considered a promising candidate for suicide gene therapy of uterine leiomyoma.

Cancer Gene Therapy by Direct Tumor Injections of a Nonviral T7 Vector Encoding a Thymidine Kinase Gene

1998 ◽  
Vol 9 (5) ◽  
pp. 729-736 ◽  
Author(s):  
Xiaozhuo Chen ◽  
Yunsheng Li ◽  
Keyong Xiong ◽  
Simona Aizicovici ◽  
Yuefeng Xie ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Thymidine Kinase ◽  
Cancer Gene Therapy ◽  
Cancer Gene ◽  
Thymidine Kinase Gene ◽  
Kinase Gene

Cancer Gene Therapy

2003 ◽  
Vol 2 (1) ◽  
pp. 51-63 ◽  
Author(s):  
Joanne T. Douglas
Keyword(s):  
Gene Therapy ◽  
Cancer Cells ◽  
Genetic Basis ◽  
Genetic Material ◽  
Cancer Gene Therapy ◽  
Successful Implementation ◽  
Cancer Gene ◽  
Targeted Interventions ◽  
Efficient Gene ◽  
Therapy Strategies

Cancer gene therapy is the transfer of genetic material to the cells of an individual with the goal of eradicating cancer cells, both in the primary tumor and metastases. Cancer gene therapy strategies exploit our expanding knowledge of the genetic basis of cancer, thereby allowing rationally targeted interventions at the molecular level. The successful implementation of cancer gene therapy in the clinic awaits the development of vectors capable of specific and efficient gene delivery to cancer cells. The first clinical applications of cancer gene therapy are likely to be in combination with conventional therapies, such as radiotherapy and immunotherapy.

scholarly journals Tissue-Specific, Tumor-Selective, Replication-Competent Adenovirus Vector for Cancer Gene Therapy

2001 ◽  
Vol 75 (7) ◽  
pp. 3314-3324 ◽  
Author(s):  
Konstantin Doronin ◽  
Mohan Kuppuswamy ◽  
Karoly Toth ◽  
Ann E. Tollefson ◽  
Peter Krajcsi ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Gene Therapy ◽  
Cancer Gene ◽  
Human Cancer Cell ◽  
Tissue Specific ◽  
Tissue Specific Promoter ◽  
Efficient Replication

ABSTRACT We have previously described two replication-competent adenovirus vectors, named KD1 and KD3, for potential use in cancer gene therapy. KD1 and KD3 have two small deletions in the E1A gene that restrict efficient replication of these vectors to human cancer cell lines. These vectors also have increased capacity to lyse cells and spread from cell to cell because they overexpress the adenovirus death protein, an adenovirus protein required for efficient cell lysis and release of adenovirus from the cell. We now describe a new vector, named KD1-SPB, which is the KD1 vector with the E4 promoter replaced by the promoter for surfactant protein B (SPB). SPB promoter activity is restricted in the adult to type II alveolar epithelial cells and bronchial epithelial cells. Because KD1-SPB has the E1A mutations, it should replicate within and destroy only alveolar and bronchial cancer cells. We show that KD1-SPB replicates, lyses cells, and spreads from cell to cell as well as does KD1 in H441 cells, a human cancer cell line where the SPB promoter is active. KD1-SPB replicates, lyses cells, and spreads only poorly in Hep3B liver cancer cells. Replication was determined by expression of the E4ORF3 protein, viral DNA accumulation, fiber synthesis, and virus yield. Cell lysis and vector spread were measured by lactate dehydrogenase release and a “vector spread” assay. In addition to Hep3B cells, KD1-SPB also did not express E4ORF3 in HT29.14S (colon), HeLa (cervix), KB (nasopharynx), or LNCaP (prostate) cancer cell lines, in which the SPB promoter is not expected to be active. Following injection into H441 or Hep3B tumors growing in nude mice, KD1-SPB caused a three- to fourfold suppression of growth of H441 tumors, similar to that seen with KD1. KD1-SPB had only a minimal effect on the growth of Hep3B tumors, whereas KD1 again caused a three- to fourfold suppression. These results establish that the adenovirus E4 promoter can be replaced by a tissue-specific promoter in a replication-competent vector. The vector has three engineered safety features: the tissue-specific promoter, the mutations in E1A that preclude efficient replication in nondividing cells, and a deletion of the E3 genes which shield the virus from attack by the immune system. KD1-SPB may have use in treating human lung cancers in which the SPB promoter is active.

A Novel Hybrid Promoter ARE-hTERT for Cancer Gene Therapy

Acta Naturae ◽  
2017 ◽  
Vol 9 (4) ◽  
pp. 66-73
Author(s):  
S. V. Kalinichenko ◽  
M. V. Shepelev ◽  
P. N. Vikhreva ◽  
I. V. Korobko
Keyword(s):  
Gene Therapy ◽  
Cancer Cells ◽  
Cytosine Deaminase ◽  
Chimeric Protein ◽  
Gene Promoter ◽  
Cancer Gene Therapy ◽  
Cancer Gene ◽  
Htert Promoter ◽  
Hybrid Promoter

describe a novel hybrid tumor-specific promoter, ARE-hTERT, composed of the human TERT gene promoter (hTERT) and the antioxidant response element (ARE) from the human GCLM gene promoter. The hybrid promoter retains the tumor specificity of the basal hTERT promoter but is characterized by an enhanced transcriptional activity in cancer cells with abnormal activation of the Nrf2 transcription factor and upon induction of oxidative stress. In the in vitro enzyme-prodrug cancer gene therapy scheme, ARE-hTERT promoter-driven expression of CD : UPRT (yeast cytosine deaminase : uracil phosphoribosyltransferase) chimeric protein induced a more pronounced death of cancer cells either upon treatment with 5-fluorouracil (5FC) alone or when 5FC was combined with chemotherapeutic drugs as compared to the hTERT promoter. The developed hybrid promoter can be considered a better alternative to the hTERT promoter in cancer gene therapy schemes.

Biodegradable nanoparticle-mediated K-ras down regulation for pancreatic cancer gene therapy

2015 ◽  
Vol 3 (10) ◽  
pp. 2163-2172 ◽  
Author(s):  
Chengbin Yang ◽  
Rui Hu ◽  
Tommy Anderson ◽  
Yucheng Wang ◽  
Guimiao Lin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Gene Therapy ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Sirna Delivery ◽  
Cancer Gene Therapy ◽  
Migration And Invasion ◽  
Cancer Gene ◽  
Pancreatic Cancer Cells ◽  
Biodegradable Nanoparticle

Biodegradable nanoparticle-mediated K-ras siRNA delivery has shown inhibition of cell proliferation, migration and invasion in pancreatic cancer cells.

A Novel Parasite-Derived Suicide Gene for Cancer Gene Therapy with Specificity for Lung Cancer Cells

2001 ◽  
Vol 12 (13) ◽  
pp. 1673-1680 ◽  
Author(s):  
Caroline Trudeau ◽  
Shala Yuan ◽  
Jacques Galipeau ◽  
Naciba Benlimame ◽  
Moulay A. Alaoui-Jamali ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gene Therapy ◽  
Cancer Cells ◽  
Suicide Gene ◽  
Cancer Gene Therapy ◽  
Lung Cancer Cells ◽  
Cancer Gene

Graphene oxide–hydroxyapatite nanocomposites effectively deliver HSV-TK suicide gene to inhibit human breast cancer growth

2018 ◽  
Vol 33 (2) ◽  
pp. 216-226 ◽  
Author(s):  
Tuck-Yun Cheang ◽  
Yi-Yan Lei ◽  
Zhan-Qiang Zhang ◽  
Hong-Yan Zhou ◽  
Run-Yi Ye ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Graphene Oxide ◽  
Gene Delivery ◽  
Cancer Cells ◽  
Transfection Efficiency ◽  
Suicide Gene ◽  
Suicide Gene Therapy ◽  
Human Breast ◽  
Kinase Gene ◽  
Ganciclovir Treatment

Gene therapy with herpes simplex virus thymidine kinase gene (HSV-TK), which is also known as “suicide” gene therapy, is effective in various tumor models. The lack of a safe and efficient gene delivery system has become a major obstacle to “suicide” gene therapy. In this study, the cytotoxicity and transfection efficiency of graphene oxide–hydroxyapatite (GO–Hap) were analyzed by MTS and flow cytometry, respectively. A series of assays were performed to evaluate the effects of GO–HAp/p-HRE/ERE-Sur-TK combined with ganciclovir treatment on growth of human breast normal and cancer cells. The results showed that GO–HAp nanocomposites effectively transfected cells with minimum toxicity. GO–HAp/p-HRE/ERE-Sur-TK combined with ganciclovir treatment inhibited the proliferation and induced cell apoptosis in cancer cells, while the cytotoxic effects are tolerable in normal breast cells. We conclude that the GO–HAp nanocomposites have significant potential as a gene delivery vector for cancer therapy.

scholarly journals The Role of Immunosuppression in the Efficacy of Cancer Gene Therapy Using Adenovirus Transfer of the Herpes Simplex Thymidine Kinase Gene

1995 ◽  
Vol 222 (3) ◽  
pp. 298-310 ◽  
Author(s):  
Ashraf A. Elshami ◽  
John C. Kucharczuk ◽  
Daniel H. Sterman ◽  
W. Roy Smythe ◽  
Harry C. Hwang ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Herpes Simplex ◽  
Thymidine Kinase ◽  
Cancer Gene Therapy ◽  
Cancer Gene ◽  
Thymidine Kinase Gene ◽  
Kinase Gene ◽  
Herpes Simplex Thymidine Kinase

Enhanced Suppression of Disulfide Cross-Linking Micelles Nanocarriers Loaded miR-145 Delivering System via Down-Regulation of MYC and FSCN1 in Colon Cancer Cells

2020 ◽  
Vol 16 (8) ◽  
pp. 1183-1195
Author(s):  
Jingming Zhai ◽  
Yanliang Zhu ◽  
Jiangbo Liu ◽  
Junling An ◽  
Yingjie Yu ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Complex Disease ◽  
Cancer Gene Therapy ◽  
Cross Linking ◽  
Cancer Gene ◽  
Colon Cancer Cells ◽  
Hct 116

Colorectal carcinoma is a complex disease accounting for adenoma tumors and an aggressive phenotype, and the third leading cause of cancer death. In the past decades, miRNAs have been associated with molecular pathways of cancer and other diseases. The dysregulated miRNAs play an inhibitory or promoting role in tumorigenesis. Therefore, restoration of tumor-suppressed microRNAs (miRNA) may offer novel therapeutic approaches for cancer treatment. Nevertheless, the poor bioavailability of miRNA due to their rapid enzymatic degradation is a critical barrier in cancer gene therapy. To overcome this dilemma, we designed disulfide cross-linking micelles (DCM) nanocarrier for delivery of miR-145 to colon cancer cells and investigated its therapeutic efficacy in vitro and in vivo. Results indicated that the presence of DCM nanocarrier loaded with miR-145 enhanced selective delivery of miR-145 and facilitated cellular uptake, significantly up-regulating miR-145 expression in HCT-116 cell lines. Consequently, the cell proliferation was inhibited by arresting cell cycle at the G1 phase. Further, apoptosis of HCT-116 cells treated with miR-145 complex nanoparticles may be via downregulation of oncogenes MYC and FSCN1, predicting regulatory targets for miR-145. These results pave the way for further investigations into the potential of miR-145 complex nanocarrier for cancer gene therapy.

Sign in / Sign up

Export Citation Format

Share Document