scholarly journals Targeting Cancer with CRISPR/Cas9-Based Therapy

2022 ◽  
Vol 23 (1) ◽  
pp. 573
Author(s):  
Katarzyna Balon ◽  
Adam Sheriff ◽  
Joanna Jacków ◽  
Łukasz Łaczmański
Keyword(s):  
Targeted Delivery ◽  
Gene Editing ◽  
Current Treatment ◽  
Cancer Type ◽  
Oncogenic Mutations ◽  
Gradual Accumulation ◽  
Selective Death ◽  
Cancerous Cells ◽  
Single Tumour ◽  
Careful Design

Cancer is a devastating condition characterised by the uncontrolled division of cells with many forms remaining resistant to current treatment. A hallmark of cancer is the gradual accumulation of somatic mutations which drive tumorigenesis in cancerous cells, creating a mutation landscape distinctive to a cancer type, an individual patient or even a single tumour lesion. Gene editing with CRISPR/Cas9-based tools now enables the precise and permanent targeting of mutations and offers an opportunity to harness this technology to target oncogenic mutations. However, the development of safe and effective gene editing therapies for cancer relies on careful design to spare normal cells and avoid introducing other mutations. This article aims to describe recent advancements in cancer-selective treatments based on the CRISPR/Cas9 system, especially focusing on strategies for targeted delivery of the CRISPR/Cas9 machinery to affected cells, controlling Cas9 expression in tissues of interest and disrupting cancer-specific genes to result in selective death of malignant cells.

scholarly journals Probiotics: A Promising Candidate for Management of Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3178
Author(s):  
Ashutosh Tripathy ◽  
Jayalaxmi Dash ◽  
Sudhakar Kancharla ◽  
Prachetha Kolli ◽  
Deviyani Mahajan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Treatment Strategies ◽  
Intestinal Barrier ◽  
World Health ◽  
Intestinal Barrier Function ◽  
Cancer Type ◽  
Prevention Therapy ◽  
Long Time ◽  
Health Organization ◽  
Cancerous Cells

Colorectal cancer (CRC) is the World’s third most frequently diagnosed cancer type. It accounted for about 9.4% mortality out of the total incidences of cancer in the year 2020. According to estimated facts by World Health Organization (WHO), by 2030, 27 million new CRC cases, 17 million deaths, and around 75 million people living with the disease will appear. The facts and evidence that establish a link between the intestinal microflora and the occurrence of CRC are quite intuitive. Current shortcomings of chemo- and radiotherapies and the unavailability of appropriate treatment strategies for CRC are becoming the driving force to search for an alternative approach for the prevention, therapy, and management of CRC. Probiotics have been used for a long time due to their beneficial health effects, and now, it has become a popular candidate for the preventive and therapeutic treatment of CRC. The probiotics adopt different strategies such as the improvement of the intestinal barrier function, balancing of natural gut microflora, secretion of anticancer compounds, and degradation of carcinogenic compounds, which are useful in the prophylactic treatment of CRC. The pro-apoptotic ability of probiotics against cancerous cells makes them a potential therapeutic candidate against cancer diseases. Moreover, the immunomodulatory properties of probiotics have created interest among researchers to explore the therapeutic strategy by activating the immune system against cancerous cells. The present review discusses in detail different strategies and mechanisms of probiotics towards the prevention and treatment of CRC.

Recent Progress in Mitochondria-Targeting-Based Nanotechnology for Cancer Treatment

Nanoscale ◽  
2021 ◽  
Author(s):  
Jingbo Qin ◽  
Ningqiang Gong ◽  
Zhihuan Liao ◽  
Shouwen Zhang ◽  
Peter S. Timashev ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Targeted Delivery ◽  
Recent Progress ◽  
Proliferation And Apoptosis ◽  
Cancerous Cells ◽  
Mitochondria Targeting

Mitochondria play critical roles in the regulation of the proliferation and apoptosis of cancerous cells. Nanosystems for targeted delivery of cargos to mitochondria for cancer treatment have attracted increasing attention...

scholarly journals Advances in the Etiology, Detection, and Clinical Management of Seborrheic Keratoses

Dermatology ◽  
2021 ◽  
pp. 1-13
Author(s):  
Mary D. Sun ◽  
Allan C. Halpern
Keyword(s):  
Therapeutic Potential ◽  
Malignant Tumors ◽  
Treatment Options ◽  
Current Treatment ◽  
Diagnostic Methods ◽  
Treatment Standards ◽  
Oncogenic Mutations ◽  
Malignant State ◽  
Underlying Mechanisms ◽  
Seborrheic Keratoses

Seborrheic keratoses (SKs) are ubiquitous, generally benign skin tumors that exhibit high clinical variability. While age is a known risk factor, the precise roles of UV exposure and immune abnormalities are currently unclear. The underlying mechanisms of this benign disorder are paradoxically driven by oncogenic mutations and may have profound implications for our understanding of the malignant state. Advances in molecular pathogenesis suggest that inhibition of Akt and APP, as well as existing treatments for skin cancer, may have therapeutic potential in SK. Dermoscopic criteria have also become increasingly important to the accurate detection of SK, and other noninvasive diagnostic methods, such as reflectance confocal microscopy and optical coherence tomography, are rapidly developing. Given their ability to mimic malignant tumors, SK cases are often used to train artificial intelligence-based algorithms in the computerized detection of skin disease. These technologies are becoming increasingly accurate and have the potential to significantly augment clinical practice. Current treatment options for SK cause discomfort and can lead to adverse post-treatment effects, especially in skin of color. In light of the discontinuation of ESKATA in late 2019, promising alternatives, such as nitric-zinc and trichloroacetic acid topicals, should be further developed. There is also a need for larger, head-to-head trials of emerging laser therapies to ensure that future treatment standards address diverse patient needs.

scholarly journals 2219

2017 ◽  
Vol 1 (S1) ◽  
pp. 59-59
Author(s):  
Shaheen Kurani ◽  
Nicolas Madigan ◽  
Karl Clark ◽  
Stephen Ekker ◽  
Nathan Staff ◽  
...  
Keyword(s):  
Cell Survival ◽  
Targeted Delivery ◽  
Transfection Efficiency ◽  
Current Treatment ◽  
Safe Harbor ◽  
Systemic Delivery ◽  
Transcription Activator ◽  
Field Methods ◽  
A Cell ◽  
The Central Nervous System

OBJECTIVES/SPECIFIC AIMS: The current treatment for amyotrophic lateral sclerosis (ALS) includes systemic delivery of neurotrophic factors (NTFs). Although this approach may seem theoretically sound, NTF efficacy within the central nervous system (CNS) is largely limited by the blood-brain barrier. Thus, a cell-based approach, which allows for targeted delivery of molecular therapies locally from the CNS, could lead to a paradigm shift in the field. METHODS/STUDY POPULATION: The Windebank and Staff group at Mayo Clinic completed a Phase I dose-escalation safety trial of autologous, adipose-derived mesenchymal stem cells (adMSCs) in an effort to move toward personalized medical treatment of ALS. The adMSCs were injected into the intrathecal space by lumbar puncture in 27 patients and the results showed an excellent safety profile across a range of doses. The team is moving forward with this idea by using gene-editing technology to develop clinical-grade, genetically modified autologous MSCs. The patient-derived adMSCs are modified at defined “safe-harbor” regions of the human genome through transcription activator-like effector nuclease (TALEN) technology. RESULTS/ANTICIPATED RESULTS: Our results show that electroporating adMSCs with plasmid DNA leads to efficient GFP or TALEN transgene expression, but yields low cell survival and a low rate of genetic modification. DISCUSSION/SIGNIFICANCE OF IMPACT: It can be concluded that: (1) TALEN technology may be used to target safe harbor loci for gene integration to produce therapeutic adMSC for ALS. (2) Primary barriers to adMSC modification are inefficient TALEN and donor template uptake, low cutting efficiency, and poor cell survival after electroporation. Future directions include optimizing the protocol to obtain 48 base pairs in the homology arms and increasing transfection efficiency.

scholarly journals Promising Nanotechnology Approaches in Treatment of Autoimmune Diseases of Central Nervous System

2020 ◽  
Vol 10 (6) ◽  
pp. 338 ◽  
Author(s):  
Maria Chountoulesi ◽  
Costas Demetzos
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Targeted Delivery ◽  
Current Treatment ◽  
Autoimmune Encephalomyelitis ◽  
Axon Damage ◽  
The Central Nervous System ◽  
Therapeutic Tools ◽  
High Bioavailability ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a chronic, autoimmune, neurodegenerative disease of the central nervous system (CNS) that yields to neuronal axon damage, demyelization, and paralysis. Although several drugs were designed for the treatment of MS, with some of them being approved in the last few decades, the complete remission and the treatment of progressive forms still remain a matter of debate and a medical challenge. Nanotechnology provides a variety of promising therapeutic tools that can be applied for the treatment of MS, overcoming the barriers and the limitations of the already existing immunosuppressive and biological therapies. In the present review, we explore literature case studies on the development of drug delivery nanosystems for the targeted delivery of MS drugs in the pathological tissues of the CNS, providing high bioavailability and enhanced therapeutic efficiency, as well as nanosystems for the delivery of agents to facilitate efficient remyelination. Moreover, we present examples of tolerance-inducing nanocarriers, being used as promising vaccines for antigen-specific immunotherapy of MS. We emphasize on liposomes, as well as lipid- and polymer-based nanoparticles. Finally, we highlight the future perspectives given by the nanotechnology field toward the improvement of the current treatment of MS and its animal model, experimental autoimmune encephalomyelitis (EAE).

scholarly journals Targeted delivery of CRISPR-Cas9 ribonucleoprotein into arthropod ovaries for heritable germline gene editing

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Duverney Chaverra-Rodriguez ◽  
Vanessa M. Macias ◽  
Grant L. Hughes ◽  
Sujit Pujhari ◽  
Yasutsugu Suzuki ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Gene Editing ◽  
Germline Gene

scholarly journals Multifunctional lipidic nanocarriers for effective therapy of glioblastoma: recent advances in stimuli-responsive, receptor and subcellular targeted approaches

2021 ◽  
Author(s):  
Manasa Manjunath Hegde ◽  
Suma Prabhu ◽  
Srinivas Mutalik ◽  
Abhishek Chatterjee ◽  
Jayant S. Goda ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Cancer Type ◽  
Stimuli Responsive ◽  
Term Survival ◽  
Oncology Research ◽  
Optimal Drug ◽  
Lipid Nanocarriers ◽  
Surface Modified

Abstract Background Glioblastoma, or glioblastoma multiforme (GBM), remains a fatal cancer type despite the remarkable progress in understanding the genesis and propagation of the tumor. Current treatment modalities, comprising mainly of surgery followed by adjuvant chemoradiation, are insufficient for improving patients' survival owing to existing hurdles, including the blood–brain barrier (BBB). In contemporary practice, the prospect of long-term survival or cure continues to be a challenge for patients suffering from GBM. This review provides an insight into the drug delivery strategies and the significant efforts made in lipid-based nanoplatform research to circumvent the challenges in optimal drug delivery in GBM. Area covered Owing to the unique properties of lipid-based nanoplatforms and advancements in clinical translation, this article describes the application of various stimuli-responsive lipid nanocarriers and tumor subcellular organelle-targeted therapy to give an idea about the strategies that can be applied to enhance site-specific drug delivery for GBM. Furthermore, active targeting of drugs via surface-modified lipid-based nanostructures and recent findings in alternative therapeutic platforms such as gene therapy, immunotherapy, and multimodal therapy have also been overviewed. Expert opinion Lipid-based nanoparticles stand out among the other nanocarriers explored for GBM drug delivery, as they support both passive and active drug targeting by crossing/bypassing the BBB at the same time minimizing toxicity and projects better pharmacological parameters. Although these nanocarriers could be a plausible choice for treating GBM, in-depth research is essential to advance neuro-oncology research and enhance outcomes in patients with brain tumors.

Colloidal Nanocarriers as Versatile Targeted Delivery Systems for Cervical Cancer

2020 ◽  
Vol 26 (40) ◽  
pp. 5174-5187 ◽  
Author(s):  
Abimanyu Sugumaran ◽  
Vishali Mathialagan
Keyword(s):  
Cervical Cancer ◽  
Side Effects ◽  
Anticancer Agents ◽  
Targeted Delivery ◽  
Metallic Nanoparticles ◽  
Polymeric Nanoparticles ◽  
Survival Rates ◽  
Cost Effective ◽  
Current Treatment ◽  
Normal Tissues

Background: The second most common malignant cancer of the uterus is cervical cancer, which is present worldwide, has a rising death rate and is predominant in developing countries. Different classes of anticancer agents are used to treat cervical carcinoma. The use of these agents results in severe untoward side-effects, toxicity, and multidrug resistance (MDR) with higher chances of recurrence and spread beyond the pelvic region. Moreover, the resulting clinical outcome remains very poor even after surgical procedures and treatment with conventional chemotherapy. Because of the nonspecificity of their use, the agents wipe out both cancerous and normal tissues. Colloidal nano dispersions have now been focusing on site-specific delivery for cervical cancer, and there has been much advancement. Methods: This review aims to highlight the problems in the current treatment of cervical cancer and explore the potential of colloidal nanocarriers for selective delivery of anticancer drugs using available literature. Results: In this study, we surveyed the role and potential of different colloidal nanocarriers in cervical cancer, such as nanoemulsion, nanodispersions, polymeric nanoparticles, and metallic nanoparticles and photothermal and photodynamic therapy. We found significant advancement in colloidal nanocarrier-based cervical cancer treatment. Conclusion: Cervical cancer-targeted treatment with colloidal nanocarriers would hopefully result in minimal toxic side effects, reduced dosage frequency, and lower MDR incidence and enhance the patient survival rates. The future direction of the study should be focused more on the regulatory barrier of nanocarriers based on clinical outcomes for cervical cancer targeting with cost-effective analysis.

scholarly journals CRISPR-Cas9 genome editing using targeted lipid nanoparticles for cancer therapy

2020 ◽  
Vol 6 (47) ◽  
pp. eabc9450 ◽  
Author(s):  
Daniel Rosenblum ◽  
Anna Gutkin ◽  
Ranit Kedmi ◽  
Srinivas Ramishetti ◽  
Nuphar Veiga ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Targeted Delivery ◽  
Gene Editing ◽  
Lipid A ◽  
Cancer Therapeutics ◽  
Intracerebral Injection ◽  
Tumor Cell Apoptosis ◽  
Potential Applications ◽  
Targeted Gene Editing

Harnessing CRISPR-Cas9 technology for cancer therapeutics has been hampered by low editing efficiency in tumors and potential toxicity of existing delivery systems. Here, we describe a safe and efficient lipid nanoparticle (LNP) for the delivery of Cas9 mRNA and sgRNAs that use a novel amino-ionizable lipid. A single intracerebral injection of CRISPR-LNPs against PLK1 (sgPLK1-cLNPs) into aggressive orthotopic glioblastoma enabled up to ~70% gene editing in vivo, which caused tumor cell apoptosis, inhibited tumor growth by 50%, and improved survival by 30%. To reach disseminated tumors, cLNPs were also engineered for antibody-targeted delivery. Intraperitoneal injections of EGFR-targeted sgPLK1-cLNPs caused their selective uptake into disseminated ovarian tumors, enabled up to ~80% gene editing in vivo, inhibited tumor growth, and increased survival by 80%. The ability to disrupt gene expression in vivo in tumors opens new avenues for cancer treatment and research and potential applications for targeted gene editing of noncancerous tissues.

scholarly journals Nanotechnology to the Rescue: Treatment Perspective for the Immune Dysregulation Observed in COVID-19

2021 ◽  
Vol 3 ◽  
Author(s):  
Angela E. Peter ◽  
B. V. Sandeep ◽  
B. Ganga Rao ◽  
V. Lakshmi Kalpana
Keyword(s):  
Drug Delivery ◽  
Signaling Pathways ◽  
Targeted Delivery ◽  
Inflammatory Diseases ◽  
Human Life ◽  
Immune Dysregulation ◽  
Current Treatment ◽  
The Body ◽  
Signaling Cascades ◽  
Great Promise

The study of the use of nanotechnology for drug delivery has been extensive. Nanomedical approaches for therapeutics; drug delivery in particular is superior to conventional methods in that it allows for controlled targeted delivery and release, higher stability, extended circulation time, minimal side-effects, and improved pharmacokinetic clearance (of the drug) form the body, to name a few. The magnitude of COVID-19, the current ongoing pandemic has been severe; it has caused widespread the loss of human life. In individuals with severe COVID-19, immune dysregulation and a rampant state of hyperinflammation is observed. This kind of an immunopathological response is detrimental and results in rapid disease progression, development of secondary infections, sepsis and can be fatal. Several studies have pin-pointed the reason for this immune dysregulation; deviations in the signaling pathways involved in the mediation and control of immune responses. In severe COVID-19 patients, many signaling cascades including JAK/STAT, NF-κB, MAPK/ERK, TGF beta, VEGF, and Notch signaling were found to be either upregulated or inactivated. Targeting these aberrant signaling pathways in conjunction with antiviral therapy will effectuate mitigation of the hyperinflammation, hypercytokinemia, and promote faster recovery. The science of the use of nanocarriers as delivery agents to modulate these signaling pathways is not new; it has already been explored for other inflammatory diseases and in particular, cancer therapy. Numerous studies have evaluated the efficacy and potential of nanomedical approaches to modulate these signaling pathways and have been met with positive results. A treatment regime, that includes nanotherapeutics and antiviral therapies will prove effective and holds great promise for the successful treatment of COVID-19. In this article, we review different nanomedical approaches already studied for targeting aberrant signaling pathways, the host immune response to SARS-CoV-2, immunopathology and the dysregulated signaling pathways observed in severe COVID-19 and the current treatment methods in use for targeting signaling cascades in COVID-19. We then conclude by suggesting that the use of nanomedical drug delivery systems for targeting signaling pathways can be extended to effectively target the aberrant signaling pathways in COVID-19 for best treatment results.

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