Potential use of RNA interference in cancer therapy

2010 ◽  
Vol 12 ◽  
Author(s):  
Connor Phalon ◽  
Donald D. Rao ◽  
John Nemunaitis
Keyword(s):  
Clinical Trials ◽  
Rna Interference ◽  
Cancer Therapy ◽  
Delivery Systems ◽  
Specific Gene ◽  
Systemic Delivery ◽  
Therapeutic Approaches ◽  
In Vivo Delivery ◽  
Potential Use

RNA interference (RNAi) is an evolutionary conserved mechanism for specific gene silencing. This mechanism has great potential for use in targeted cancer therapy. Understanding the RNAi mechanism has led to the development of several novel RNAi-based therapeutic approaches currently in the early phases of clinical trials. It remains difficult to effectively deliver the nucleic acids required in vivo to initiate RNAi, and intense effort is under way in developing effective and targeted systemic delivery systems for RNAi. Description of in vivo delivery systems is not the focus of this review. In this review, we cover the rationale for pursuing personalised cancer therapy with RNAi, briefly review the mechanism of each major RNAi therapeutic technique, summarise and sample recent results with animal models applying RNAi for cancer, and provide an update on current clinical trials with RNAi-based therapeutic agents for cancer therapy. RNAi-based cancer therapy is still in its infancy, and there are numerous obstacles and issues that need to be resolved before its application in personalised therapy focusing on patient-cancer-specific targets can become standard cancer treatment, either alone or in combination with other treatments.

Exploring Promises of siRNA in Cancer Therapeutics

2020 ◽  
Vol 16 (1) ◽  
pp. 29-35
Author(s):  
Mahima Kaushik ◽  
Rddhima Raghunand ◽  
Shobhit Maheshwari
Keyword(s):  
Clinical Trials ◽  
Rna Interference ◽  
Cancer Therapy ◽  
Biomedical Applications ◽  
Cancer Therapeutics ◽  
Small Interfering Rnas ◽  
Polymeric Carriers ◽  
Drug Treatments ◽  
Anticancer Treatment

Since the discovery of the RNA interference (RNAi) in 2006, several attempts have been made to use it for designing and developing drug treatments for a variety of diseases, including cancer. In this mini-review, we focus on the potential of small interfering RNAs (siRNA) in anticancer treatment. We first describe the significant barriers that exist on the path to clinical application of siRNA drugs. Then the current delivery approaches of siRNAs using lipids, polymers, and, in particular, polymeric carriers that overcome the aforementioned obstacles have been reviewed. Also, few siRNA mediated drugs currently in clinical trials for cancer therapy, and a collated list of siRNA databases having a qualitative and/ or quantitative summary of the data in each database have been briefly mentioned. This mini review aims to facilitate our understanding about the siRNA, their delivery systems and the possible barriers in their in vivo usage for biomedical applications.

scholarly journals Delivery Systems for the Direct Application of siRNAs to Induce RNA Interference (RNAi) In Vivo

2006 ◽  
Vol 2006 ◽  
pp. 1-15 ◽  
Author(s):  
Achim Aigner
Keyword(s):  
Rna Interference ◽  
Sirna Delivery ◽  
Critical Factor ◽  
Delivery Systems ◽  
Tumor Xenograft ◽  
Target Cells ◽  
Specific Gene ◽  
Mouse Tumor ◽  
Small Interfering Rnas

RNA interference (RNAi) is a powerful method for specific gene silencing which may also lead to promising novel therapeutic strategies. It is mediated through small interfering RNAs (siRNAs) which sequence-specifically trigger the cleavage and subsequent degradation of their target mRNA. One critical factor is the ability to deliver intact siRNAs into target cells/organs in vivo. This review highlights the mechanism of RNAi and the guidelines for the design of optimal siRNAs. It gives an overview of studies based on the systemic or local application of naked siRNAs or the use of various nonviral siRNA delivery systems. One promising avenue is the the complexation of siRNAs with the polyethylenimine (PEI), which efficiently stabilizes siRNAs and, upon systemic administration, leads to the delivery of the intact siRNAs into different organs. The antitumorigenic effects of PEI/siRNA-mediated in vivo gene-targeting of tumor-relevant proteins like in mouse tumor xenograft models are described.

scholarly journals siRNA Delivery Technology for Cancer Therapy: Promise and Challenges

2019 ◽  
Author(s):  
Fateme Karimi Dermani ◽  
Farid Azizi Jalilian ◽  
Hossein Hossienkhani ◽  
Razieh Ezati ◽  
Razieh Amini
Keyword(s):  
Cancer Therapy ◽  
Sirna Delivery ◽  
Delivery Systems ◽  
Therapeutic Interventions ◽  
Great Promise ◽  
Specific Gene ◽  
Small Interfering Rnas ◽  
Systemic Delivery ◽  
New Class ◽  
Delivery Technology

Abstract- Small interfering RNAs (siRNA) technology has shown great promise as a new class of therapeutic interventions for the treatment of cancer and other diseases. It is a remarkable endogenous pathway that can regulate sequence-specific gene silencing. Despite the excitement about possible applications of this biological process for sequence-specific gene regulation, the major limitations against the use of siRNA-based therapeutics are their rapid degradation by serum nuclease, poor cellular uptake, and rapid renal clearance following systemic delivery, off-target effects and the induction of immune responses. Many researchers have tried to overcome these limitations by developing nuclease-resistant chemically-modified siRNAs and a variety of synthetic and natural biodegradable lipids and polymers to enhance the efficacy and safety profiles of siRNA delivery. Ideal siRNA-based delivery systems for cancer therapy must be clinically suitable, safe and effective. In this review, we introduce the greatest challenges in achieving efficient RNAi delivery and discuss design criteria and various delivery strategies for cancer therapy, including chemical modifications, lipid-based nano-vectors, polymer-mediated delivery systems, conjugate delivery systems, and others.

scholarly journals Targeting Sphingolipids for Cancer Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Osmel Companioni ◽  
Cristina Mir ◽  
Yoelsis Garcia-Mayea ◽  
Matilde E. LLeonart
Keyword(s):  
Clinical Trials ◽  
Cell Death ◽  
Cancer Therapy ◽  
Preclinical Studies ◽  
Hepatic Toxicity ◽  
Multiple Cancers ◽  
Extensive Class ◽  
Effective Drugs

Sphingolipids are an extensive class of lipids with different functions in the cell, ranging from proliferation to cell death. Sphingolipids are modified in multiple cancers and are responsible for tumor proliferation, progression, and metastasis. Several inhibitors or activators of sphingolipid signaling, such as fenretinide, safingol, ABC294640, ceramide nanoliposomes (CNLs), SKI-II, α-galactosylceramide, fingolimod, and sonepcizumab, have been described. The objective of this review was to analyze the results from preclinical and clinical trials of these drugs for the treatment of cancer. Sphingolipid-targeting drugs have been tested alone or in combination with chemotherapy, exhibiting antitumor activity alone and in synergism with chemotherapy in vitro and in vivo. As a consequence of treatments, the most frequent mechanism of cell death is apoptosis, followed by autophagy. Aslthough all these drugs have produced good results in preclinical studies of multiple cancers, the outcomes of clinical trials have not been similar. The most effective drugs are fenretinide and α-galactosylceramide (α-GalCer). In contrast, minor adverse effects restricted to a few subjects and hepatic toxicity have been observed in clinical trials of ABC294640 and safingol, respectively. In the case of CNLs, SKI-II, fingolimod and sonepcizumab there are some limitations and absence of enough clinical studies to demonstrate a benefit. The effectiveness or lack of a major therapeutic effect of sphingolipid modulation by some drugs as a cancer therapy and other aspects related to their mechanism of action are discussed in this review.

An Overview of nano delivery systems for targeting RNA interference-based therapy in ulcerative colitis

2021 ◽  
Vol 27 ◽  
Author(s):  
Iman Alfagih ◽  
Basmah Aldosari ◽  
Bushra AlQuadeib ◽  
Alanood Almurshedi ◽  
Murtaza Tambuwala
Keyword(s):  
Ulcerative Colitis ◽  
Rna Interference ◽  
Protein Expression ◽  
Messenger Rna ◽  
Delivery Systems ◽  
Target Cells ◽  
Intracellular Space ◽  
Therapeutic Benefits ◽  
Negative Effect

: Ulcerative colitis (UC) is one of the main subtypes of inflammatory bowel disease. UC has a negative effect on patients’ quality of life, and it is an important risk factor for the development of colitis-associated cancer. Patients with UC need to take medications for their entire life because no permanent cure is available. Therefore, approaches that target messenger RNA (mRNA) of proinflammatory cytokines or anti-inflammatory cytokines are needed to improve the safety of UC therapy and promote intestinal mucosa recovery. The major challenge facing RNA interference-based therapy is the delivery of RNA molecules to the intracellular space of target cells. Moreover, nonspecific and systemic protein expression inhibition can result in adverse effects and less therapeutic benefits. Thus, it is important to develop an efficient delivery strategy targeting the cytoplasm of target cells to avoid side effects caused by off-target protein expression inhibition. This review focuses on the most recent advances in the targeted nano delivery systems of siRNAs and mRNA that have shown in vivo efficacy.

scholarly journals Pharmacophore hybridisation and nanoscale assembly to discover self-delivering lysosomotropic new-chemical entities for cancer therapy

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhao Ma ◽  
Jin Li ◽  
Kai Lin ◽  
Mythili Ramachandran ◽  
Dalin Zhang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Therapy ◽  
Self Assembly ◽  
The Self ◽  
Single Drug ◽  
Drug Nanoparticles ◽  
Lysosomal Dysfunction ◽  
New Chemical Entities ◽  
Autophagy Inhibition

Abstract Integration of the unique advantages of the fields of drug discovery and drug delivery is invaluable for the advancement of drug development. Here we propose a self-delivering one-component new-chemical-entity nanomedicine (ONN) strategy to improve cancer therapy through incorporation of the self-assembly principle into drug design. A lysosomotropic detergent (MSDH) and an autophagy inhibitor (Lys05) are hybridised to develop bisaminoquinoline derivatives that can intrinsically form nanoassemblies. The selected BAQ12 and BAQ13 ONNs are highly effective in inducing lysosomal disruption, lysosomal dysfunction and autophagy blockade and exhibit 30-fold higher antiproliferative activity than hydroxychloroquine used in clinical trials. These single-drug nanoparticles demonstrate excellent pharmacokinetic and toxicological profiles and dramatic antitumour efficacy in vivo. In addition, they are able to encapsulate and deliver additional drugs to tumour sites and are thus promising agents for autophagy inhibition-based combination therapy. Given their transdisciplinary advantages, these BAQ ONNs have enormous potential to improve cancer therapy.

In Vivo Delivery of Silica Nanorattle Encapsulated Docetaxel for Liver Cancer Therapy with Low Toxicity and High Efficacy

ACS Nano ◽  
2010 ◽  
Vol 4 (11) ◽  
pp. 6874-6882 ◽  
Author(s):  
Linlin Li ◽  
Fangqiong Tang ◽  
Huiyu Liu ◽  
Tianlong Liu ◽  
Nanjing Hao ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Liver Cancer ◽  
High Efficacy ◽  
Low Toxicity ◽  
Silica Nanorattle ◽  
In Vivo Delivery

scholarly journals In Vivo Delivery Systems for Therapeutic Genome Editing

2016 ◽  
Vol 17 (5) ◽  
pp. 626 ◽  
Author(s):  
Luyao Wang ◽  
Fangfei Li ◽  
Lei Dang ◽  
Chao Liang ◽  
Chao Wang ◽  
...  
Keyword(s):  
Genome Editing ◽  
Delivery Systems ◽  
In Vivo Delivery

scholarly journals In vivo Genome Editing Therapeutic Approaches for Neurological Disorders: Where Are We in the Translational Pipeline?

2021 ◽  
Vol 15 ◽  
Author(s):  
Pablo Lubroth ◽  
Gaia Colasante ◽  
Gabriele Lignani
Keyword(s):  
Clinical Trials ◽  
Genome Editing ◽  
Neurological Disorders ◽  
Therapeutic Approaches ◽  
Translational Neuroscience ◽  
Cns Disorders ◽  
Neuroscience Research ◽  
Biotechnology Companies

In vivo genome editing tools, such as those based on CRISPR, have been increasingly utilized in both basic and translational neuroscience research. There are currently nine in vivo non-CNS genome editing therapies in clinical trials, and the pre-clinical pipeline of major biotechnology companies demonstrate that this number will continue to grow. Several biotechnology companies commercializing in vivo genome editing and modification technologies are developing therapies for CNS disorders with accompanying large partnering deals. In this review, the authors discuss the current genome editing and modification therapy pipeline and those in development to treat CNS disorders. The authors also discuss the technical and commercial limitations to translation of these same therapies and potential avenues to overcome these hurdles.

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