SiRNA Delivery for Cancer Therapy: Challenges and Future Perspective by Suvadeep Sen in Advancements in Bioequivalence & Bioavailability
https://crimsonpublishers.com/abb/fulltext/ABB.000518.php
siRNA based drug delivery is used quite commonly in biological research. Depending upon the requirements suitable delivery system is selected, few of which are discussed here.
RNA interference (RNAi) is a biological process in which RNA molecules inhibit gene expression, typically by causing the destruction of specific mRNA molecules. Two types of small ribonucleic acid (RNA) molecules – microRNA (miRNA) and small interfering RNA (siRNA) – are central to RNA interference.
Delivering Small interfering RNA or si-RNA molecules in-vivo to treat diseases. Definitions, Approaches, Barriers, Solutions, Delivery systems, and more.
With an overview on gene delivery systems and philosophy.
Mirna biogenesis, mechanism of action, isolation protocol, and quantification...SAIMA BARKI
The concise SlideShare presentation on the miRNA biogenesis, nomenclature, specific isolation protocols, the use of novel primers for preamplification purpose, and the comparison of different methods, qPCR based quantification along the guidance of the choice of sample and a novel technique for the different clinical samples.
microRNA for Clinical Research and Tumor AnalysisBioGenex
The discovery of microRNAs [miRNAs] has been one of the defining developments in cancer biology over the past decade. miRNAs are short, single stranded 20-22 nucleotide long, non-coding RNAs that regulate gene expression and have fundamental roles in Cancer growth and metastasis. miRNAs exert their function via base pairing with complementary mRNA molecules, resulting in gene silencing via transcriptional repression or target degradation. BioGenex solved the inherent difficulties in visualizing miRNAs in spatial context by using a propriety technology to synthesize modified, high-affinity oligonucleotides, labelling miRNA probes with multiple reporter molecules and developing a fully-integrated miRNA-ISH workflow solution allowing high throughput analysis of miRNA in the spatial context.
Functional Analysis of miRNA: miRNA and its Role in Human Disease Webinar Ser...QIAGEN
This slideshow highlights the use of miRNA mimics, inhibitors and target protectors to increase, decrease and adjust the cellular concentration of miRNA and disrupt specific miRNA–mRNA interactions. A ready-to-use screening tool for identifying miRNA targets and info on how to predict mRNA targets using miRNA expression data are also highlighted.
TARGETED DRUG DELIVERY SYSTEM IN CANCER THERAPEUTICS: WITH SPECIAL FOCUS ON S...AnkushSharma400
Due to the mutations in the genes, cancer occurs and propagates to the other areas of the human body. The mutation in the tumor suppressor gene, as well as the oncogene, leads to the growth of a tumor. The RNA interference (RNAi) targets these genes by inducing gene silencing. Gene
silencing has been an attractive approach to stop the growth of cancer cells after the detection of RNA
interference (RNAi) in the animal cells.
siRNA based drug delivery is used quite commonly in biological research. Depending upon the requirements suitable delivery system is selected, few of which are discussed here.
RNA interference (RNAi) is a biological process in which RNA molecules inhibit gene expression, typically by causing the destruction of specific mRNA molecules. Two types of small ribonucleic acid (RNA) molecules – microRNA (miRNA) and small interfering RNA (siRNA) – are central to RNA interference.
Delivering Small interfering RNA or si-RNA molecules in-vivo to treat diseases. Definitions, Approaches, Barriers, Solutions, Delivery systems, and more.
With an overview on gene delivery systems and philosophy.
Mirna biogenesis, mechanism of action, isolation protocol, and quantification...SAIMA BARKI
The concise SlideShare presentation on the miRNA biogenesis, nomenclature, specific isolation protocols, the use of novel primers for preamplification purpose, and the comparison of different methods, qPCR based quantification along the guidance of the choice of sample and a novel technique for the different clinical samples.
microRNA for Clinical Research and Tumor AnalysisBioGenex
The discovery of microRNAs [miRNAs] has been one of the defining developments in cancer biology over the past decade. miRNAs are short, single stranded 20-22 nucleotide long, non-coding RNAs that regulate gene expression and have fundamental roles in Cancer growth and metastasis. miRNAs exert their function via base pairing with complementary mRNA molecules, resulting in gene silencing via transcriptional repression or target degradation. BioGenex solved the inherent difficulties in visualizing miRNAs in spatial context by using a propriety technology to synthesize modified, high-affinity oligonucleotides, labelling miRNA probes with multiple reporter molecules and developing a fully-integrated miRNA-ISH workflow solution allowing high throughput analysis of miRNA in the spatial context.
Functional Analysis of miRNA: miRNA and its Role in Human Disease Webinar Ser...QIAGEN
This slideshow highlights the use of miRNA mimics, inhibitors and target protectors to increase, decrease and adjust the cellular concentration of miRNA and disrupt specific miRNA–mRNA interactions. A ready-to-use screening tool for identifying miRNA targets and info on how to predict mRNA targets using miRNA expression data are also highlighted.
TARGETED DRUG DELIVERY SYSTEM IN CANCER THERAPEUTICS: WITH SPECIAL FOCUS ON S...AnkushSharma400
Due to the mutations in the genes, cancer occurs and propagates to the other areas of the human body. The mutation in the tumor suppressor gene, as well as the oncogene, leads to the growth of a tumor. The RNA interference (RNAi) targets these genes by inducing gene silencing. Gene
silencing has been an attractive approach to stop the growth of cancer cells after the detection of RNA
interference (RNAi) in the animal cells.
Chemical structural-advances-and-hurdles-to-clinical-translation-of-rn ai-the...Al Baha University
RNAi can wipe out the disease-causing proteins from being translated. Now RNAi technique has become a powerful tool for basic research to selectively knock down gene expression in vitro and in vivo. At the same time, both scientific and industrial communities started to develop RNAi therapeutics as the next class of drugs for treating a variety of genetic disorders, such as cancer and other diseases that are particularly hard to be addressed by current treatment strategies.
Gene therapy is now bringing a revolutionary treatment options to most of genetic related diseases including cancers, offering the theoretical advantage of the possibility of achieving the therapeutic goal by a single treatment.
Clustered regularly interspaced short palindromic repeat is a recent genome-editing approach have attracted significant attention among the researchers due to their potential to cure all genetic related diseases including cancer by editing the genome in a way based on RNA-guided nuclease
Sticky siRNAs targeting survivin and cyclin B1 exert an antitumoral effect on...Enrique Moreno Gonzalez
Melanoma represents one of the most aggressive and therapeutically challenging malignancies as it often gives rise to metastases and develops resistance to classical chemotherapeutic agents. Although diverse therapies have been generated, no major improvement of the patient prognosis has been noticed. One promising alternative to the conventional therapeutic approaches currently available is the inactivation of proteins essential for survival and/or progression of melanomas by means of RNA interference. Survivin and cyclin B1, both involved in cell survival and proliferation and frequently deregulated in human cancers, are good candidate target genes for siRNA mediated therapeutics.
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...JohnJulie1
Lung cancer is the second common malignancy and the most aggressive cancer worldwide with late diagnosis and poor prognosis. The search for biomarkers that promote early diagnosis and improve therapeutic strategies focuses to the understanding of the mechanisms underlying cancer development and progression. The deregulation of gene expression is one of the cancer hallmarks reflected to the stability...
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...AnonIshanvi
Lung cancer is the second common malignancy and the most aggressive cancer worldwide with late diagnosis and poor prognosis. The search for biomarkers that promote early diagnosis and improve therapeutic strategies focuses to the understanding of the mechanisms underlying cancer development and progression
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...daranisaha
Lung cancer is the second common malignancy and the most aggressive cancer worldwide with late diagnosis and poor prognosis. The search for biomarkers that promote early diagnosis and improve therapeutic strategies focuses to the understanding of the mechanisms underlying cancer development and progression. The deregulation of gene expression is one of the cancer hallmarks reflected to the stability...
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...EditorSara
Lung cancer is the second common malignancy and the most aggressive cancer worldwide with late diagnosis and poor prognosis. The search for biomarkers that promote early diagnosis and improve therapeutic strategies focuses to the understanding of the mechanisms underlying cancer development and progression. The deregulation of gene expression is one of the cancer hallmarks reflected to the stability..
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...NainaAnon
Lung cancer is the second common malignancy and the most aggressive cancer worldwide with late diagnosis and poor prognosis. The search for biomarkers that promote early diagnosis and improve therapeutic strategies focuses to the understanding of the mechanisms underlying cancer development and progression. The deregulation of gene expression is one of the cancer hallmarks reflected to the stability...
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...semualkaira
Lung cancer is the second common malignancy and the most aggressive cancer worldwide with late diagnosis and poor prognosis. The search for biomarkers that promote early diagnosis and improve therapeutic strategies focuses to the understanding of the mechanisms underlying cancer development and progression. The deregulation of gene expression is one of the cancer hallmarks reflected to the stability...
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...semualkaira
Lung cancer is the second common malignancy and the most aggressive cancer worldwide with late diagnosis and poor prognosis. The search for biomarkers that promote early diagnosis and improve therapeutic strategies focuses to the understanding of the mechanisms underlying cancer development and progression. The deregulation of gene expression is one of the cancer hallmarks reflected to the stability..
The aim of this study was to investigate the effect of malaria on liver functions in known falciparum and vivax malaria patents’ this a hospital-based study, which was carried out at Atbara and Berber towns. A total of 60 samples were included in this study out of which 25 sample of patients with falciparum malaria and 25 sample of patient s’ with vivax malaria and 10 control. Liver function test certainly (ALT) and bilirubin tests were estimated by standard method.
The theories of Ying-Yang, Zang-Fu, the Five Elements and pattern identification in the Traditional Chinese Medicine (TCM) are unique and different from those theories of the Western medicine. Qi stagnation and Blood deficiency can block the channels to cause pain in menstruation. Issues like processing of Chinese herbs, side effects and interactions of TCM herbs and Wester medications need considerations in the integration of these two medicines.
Background: Anemia is a common Feature of chronic kidney disease, but the management of anemia in children is complex. Erythropoietin and Supplemental iron are used to maintain hemoglobin levels. The aim of this study to determine the Frequency of anemia and possible Risk Factors Among children with End stage renal disease.
Methods: A total of 96 children, 61males (63.5%) and 35 Females (36.5%), were attended at hemodialysis units in Khartoum state were enrolled in the study and Frequency of anemia was estimated by analyzing CBC on blood counter (sysmex). The concentration of iron profile, C-reactive protein and parathyroid hormone was measured using COBAS INTEGRA 400 PLUS and COBAS E411.
Results: 99% of children were anemic, 4.17% of them were suffering from iron deficiency anemia and there are other causes contributing to anemia in ESRD patients which are inflammation and hyperparathyroidism.
Conclusion: The prevalence of anemia in children on hemodialysis in Sudan appears to be higher than that reported in other studies despite extensive use of rHuEPO and iron supplementation.
Prevalence of Cryptosporidiosis Among Selected Group of Sudanese Patients by Mosab Nouraldein Mohammed Hamad in Advancements in Bioequivalence & Bioavailability
An Exploration of Acupuncture Treatment to Meniere’s Disease by Tong Zheng Hong by Advancements in Bioequivalence & Bioavailability
Yin-Yang balance is absolutely the unique concept of traditional Chinese medicine (TCM) that distinguishes TCM from the Western medicine. A disease indicates a loss of the balance of Yin-Yang. The research shows acupuncture combined with western medicine comprehensive treatment (WMCT) can be more effective for the symptoms of Meniere’s disease such as vertigo and dizziness, but it remains uncertain whether acupuncture is good for hearing loss.
In Silico Study on Tea Flavanoids as Anticlastogens by Manash Pratim Sarma in Advancements in Bioequivalence & Bioavailability
The interaction of flavonoids of tea extract with different histone proteins member of bone marrow of Swiss mice in silico were satisfactory, and all the interaction (Docking using Hex 5.1) were found to have very low entropy values indicative of strong interaction.
Antibiotic Sensitivity Pattern of Bacteria Isolated from Semen of Male Patients with Infertility Attending Murtala Muhammad Specialist Hospital Kano, Nigeria by Muhammad Ali in Advancements in Bioequivalence & Bioavailability
https://crimsonpublishers.com/abb/fulltext/ABB.000519.php
Review on Genetic Engineering in Castor Bean by Yin Xuegui in Advancements in Bioequivalence & Bioavailability
https://crimsonpublishers.com/abb/fulltext/ABB.000516.php
Crystal Engineering Applied to the Development of Novel Pharmaceutical Solid Forms with Improved Bioavailability: the Co Crystals Case by Javier Ellena in Advancements in Bioequivalence & Bioavailability
Pharmaceutical co crystal technology has emerged as a promising strategy to enhance bioavailability of poorly water soluble drugs. This mini review presents a brief overview of pharmaceutical co crystals with particular focus on co crystal design, characterization techniques and impacts on drug bioavailability.
https://crimsonpublishers.com/abb/fulltext/ABB.000514.php
Allometry Scalling in Drug Development by Murugesh Kandasamy in Advancements in Bioequivalence & Bioavailability
Allometry is about the study of body size and its outcomes, it is described as ‘by a different measure’, and in allometric system the proportions are changed in a regular fashion [1]. Allometry, which is the oldest of the approaches and still widely applied in biology, is concerned with the study of the relationship between the size and function of components of the body and growth or size of the whole body [2]. Alternatively, to study the species change in a specific factor which correlates with difference in size of the species. Allometry is centered on the prediction (an exact prediction) by considering the physiological, anatomical and biochemical parallels among animals, which can be explained by mathematical models. It is now an established fact that many physiological processes and size of the organ that exhibit a power-law relationship with the body weight of the species. This relationship is defined as the scientific source of allometric scaling [3,4].
https://crimsonpublishers.com/abb/fulltext/ABB.000512.php
Isolation and Evaluation of Antibiotic Resistivity Pattern of Faecal Coliforms Bacteria Isolated From River Wudil Kano, Nigeria by Ali M in Advancements in Bioequivalence & Bioavailability
Water borne diseases has been a major public health concern in Nigeria. This study was conducted to identify and evaluate the antibiotic resistivity pattern of faecal coliforms bacteria isolated from River Wudil in Wudil Local Government Area of Kano State, Nigeria. Four (4) water samples from different part of the river were collected for the study. The bacteriological and physicochemical analyses performed were in accordance with standard procedures. Antibiotic susceptibility patterns of the bacterial isolates were determined using modified Kirby Bauer method. The result of the study revealed that the physicochemical properties of the river are within the WHO and NIS standard.
https://crimsonpublishers.com/abb/fulltext/ABB.000509.php
Critical Review on Thalassemia: Types, Symptoms and Treatment by Hamidreza Shirzadfar in Advancements in Bioequivalence & Bioavailability
Thalassemia is a genetic blood disorder where the normal hemoglobin protein is produced in lower amounts than usual and share in common one feature. This means it is passed down from one or both parents through their genes. People with Thalassemia are not able to make enough normal hemoglobin, which causes severe anemia. Hemoglobin is found in red blood cells and carries oxygen to all parts of organ in the body; therefore organs are unable to function properly. There are 30 million carriers and approximately 10000 children are born with the disease every year in the world. There are two main classes of thalassemia, Different genes are affected for each type in your body. α and β, in which the α-globin and β-globin genes are involved. In this study we will generally explain thalassemia disease, types of it and its treatment.
https://crimsonpublishers.com/abb/fulltext/ABB.000507.php
Approaches for Bioequivalence Assessment of Topical Dermatological Formulations by Syed Arman Rabbani in Advancements in Bioequivalence & Bioavailability
https://crimsonpublishers.com/abb/fulltext/ABB.000503.php
CHAPTER 1 SEMESTER V PREVENTIVE-PEDIATRICS.pdfSachin Sharma
This content provides an overview of preventive pediatrics. It defines preventive pediatrics as preventing disease and promoting children's physical, mental, and social well-being to achieve positive health. It discusses antenatal, postnatal, and social preventive pediatrics. It also covers various child health programs like immunization, breastfeeding, ICDS, and the roles of organizations like WHO, UNICEF, and nurses in preventive pediatrics.
R3 Stem Cells and Kidney Repair A New Horizon in Nephrology.pptxR3 Stem Cell
R3 Stem Cells and Kidney Repair: A New Horizon in Nephrology" explores groundbreaking advancements in the use of R3 stem cells for kidney disease treatment. This insightful piece delves into the potential of these cells to regenerate damaged kidney tissue, offering new hope for patients and reshaping the future of nephrology.
CHAPTER 1 SEMESTER V - ROLE OF PEADIATRIC NURSE.pdfSachin Sharma
Pediatric nurses play a vital role in the health and well-being of children. Their responsibilities are wide-ranging, and their objectives can be categorized into several key areas:
1. Direct Patient Care:
Objective: Provide comprehensive and compassionate care to infants, children, and adolescents in various healthcare settings (hospitals, clinics, etc.).
This includes tasks like:
Monitoring vital signs and physical condition.
Administering medications and treatments.
Performing procedures as directed by doctors.
Assisting with daily living activities (bathing, feeding).
Providing emotional support and pain management.
2. Health Promotion and Education:
Objective: Promote healthy behaviors and educate children, families, and communities about preventive healthcare.
This includes tasks like:
Administering vaccinations.
Providing education on nutrition, hygiene, and development.
Offering breastfeeding and childbirth support.
Counseling families on safety and injury prevention.
3. Collaboration and Advocacy:
Objective: Collaborate effectively with doctors, social workers, therapists, and other healthcare professionals to ensure coordinated care for children.
Objective: Advocate for the rights and best interests of their patients, especially when children cannot speak for themselves.
This includes tasks like:
Communicating effectively with healthcare teams.
Identifying and addressing potential risks to child welfare.
Educating families about their child's condition and treatment options.
4. Professional Development and Research:
Objective: Stay up-to-date on the latest advancements in pediatric healthcare through continuing education and research.
Objective: Contribute to improving the quality of care for children by participating in research initiatives.
This includes tasks like:
Attending workshops and conferences on pediatric nursing.
Participating in clinical trials related to child health.
Implementing evidence-based practices into their daily routines.
By fulfilling these objectives, pediatric nurses play a crucial role in ensuring the optimal health and well-being of children throughout all stages of their development.
Health Education on prevention of hypertensionRadhika kulvi
Hypertension is a chronic condition of concern due to its role in the causation of coronary heart diseases. Hypertension is a worldwide epidemic and important risk factor for coronary artery disease, stroke and renal diseases. Blood pressure is the force exerted by the blood against the walls of the blood vessels and is sufficient to maintain tissue perfusion during activity and rest. Hypertension is sustained elevation of BP. In adults, HTN exists when systolic blood pressure is equal to or greater than 140mmHg or diastolic BP is equal to or greater than 90mmHg. The
Antibiotic Stewardship by Anushri Srivastava.pptxAnushriSrivastav
Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
According to WHO,
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials
In 1996, John McGowan and Dale Gerding first applied the term antimicrobial stewardship, where they suggested a causal association between antimicrobial agent use and resistance. They also focused on the urgency of large-scale controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis.
Antimicrobial Stewardship(AMS) refers to the optimal selection, dosing, and duration of antimicrobial treatment resulting in the best clinical outcome with minimal side effects to the patients and minimal impact on subsequent resistance.
According to the 2019 report, in the US, more than 2.8 million antibiotic-resistant infections occur each year, and more than 35000 people die. In addition to this, it also mentioned that 223,900 cases of Clostridoides difficile occurred in 2017, of which 12800 people died. The report did not include viruses or parasites
VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
![Mohana Mukherjee1
and Suvadeep Sen2
*
1
Department of Chemical Engineering, IIT Bombay, India
2
Critical care medicine, Apollo Hospital, India
*Corresponding author: Suvadeep Sen, Junior consultant, Critical care medicine, Apollo Hospital, Navi Mumbai, Maharashtra, India
Submission: May 28, 2018; Published: July 18, 2018
SiRNA Delivery for Cancer Therapy: Challenges
and Future Perspective
Introduction
Cancer is a global public health problem. Global estimation
from WHO fact sheet revealed that nearly 1 in 6 deaths occur due to
cancer [1]. There are various aspects of treatment of cancers. The
three arms of cancer treatment are chemotherapy, radiotherapy
and surgical resection. Although, in last few decades, we have
witnessed discovery of various new chemotherapeutic drugs and
surgical advancements, the three major disadvantages of all this
treatment modalities remained to be their side effects, expenses,
sub-optimal and sometime dismal effects. siRNA nanotherapeutics
is one of the new recent advancement in this field. In current review
we will discuss various advantages and potential role of siRNA in
cancer therapy.
SiRNA and Post Transcriptional Gene Silencing
RNA interference is a cellular process where the undesired
gene expression can be silenced by degrading of that undesired
mRNA. siRNA is small double stranded RNA about 21 nucleotides
long with 3’ overhang at each end that regulates gene or genome.
Three mechanisms were investigated that leads the overall RNA
interference,
A. changes in heterochromatin formation
B. Inhibition of translation of target mRNA
C. Degradation of the target mRNA.
Second and third phenomena are mostly explored [2]. After
entering to the cells, the double stranded RNA cleaved by an enzyme
known as DICER and 20 to 22 nucleotide long siRNA formed. The
source of the double stranded RNA can be viral genome, bacterial
DNA or synthetic RNA. Later, the double strand of the siRNA is
separated by helicase enzyme and the antisense strand binds to
the RNA induced silencing complex (RISC). RISC carries the siRNA
to the target mRNA site and degrades the mRNA. Degradation of
mRNA inhibits the gene expression.
Advantages of SiRNA Therapeutics in Cancer Treatment
Anticancer chemotherapeutic agents mainly exert their affect
either by impeding DNA or RNA synthesis, or by inducing their
destruction or arresting cell cycle at particular stage. This leads to
programmedcelldeathknownasapoptosis.Themajordisadvantage
of this treatment is that, the drugs do not differentiate between
the healthy and cancer cells and thus affects non -cancerous cells
also, which leads to their side effect. siRNA on the other hand has
several potential advantages in this respect. Firstly, siRNA causes
target specific gene silencing through RNA interference system.
The risk of teratogenicity and mutation is less as it inhibits post
transcriptional gene expression and does not interact with DNA [3].
Another important advantage of siRNA is its high efficacy. Several
copies of siRNA can suppress the gene expression in a single cancer
cell. siRNA binds by complementary base pairing that restricts the
Mini Review
Advancements in
Bioequivalence & BioavailabilityC CRIMSON PUBLISHERS
Wings to the Research
1/3Copyright © All rights are reserved by Suvadeep Sen.
Volume - 1 Issue - 4
Abstract
Cancer is one of the leading causes of death across the globe. Despite advancement of conventional treatments, the safety and efficacy of various
chemotherapeutic drugs remained questionable. Recent advances in biotechnology and discovery of siRNA and RNA interference mechanism has
brought a new light in more specific and targeted treatment of malignant tissue. Important advantage of siRNA-based therapy is its target specificity
and safety, but disadvantage is to build an appropriate vehicle for its delivery into target site. Various phase I and II clinical trials are under way to test
the efficacy of this new modality of treatment.
Keywords: SiRNA; RNA interference; Cancer therapy
Abbreviations: SiRNA: Small Interfering Ribonucleic Acid; WHO: World Health Organization; RNA: Ribonucleic Acid; DNA: Deoxyribonucleic Acid;
RISC: RNA Induced Silencing Complex; Mrna: Messenger Ribonucleic Acid; VEGF: Vascular Endothelial Growth Factor; KSP: Kinesin Spindle Protein;
PKN3: Protein Kinase N3; BCL-2: B-Cell Lymphoma 2; Kda: Kilo Dalton](https://image.slidesharecdn.com/abb-190204094600/85/Crimson-Publishers-SiRNA-Delivery-for-Cancer-Therapy-Challenges-and-Future-Perspective-1-320.jpg)
![Advancements Bioequiv Availab Copyright © Suvadeep Sen
2/4
How to cite this article: Mohana M, Suvadeep S. SiRNA Delivery for Cancer Therapy: Challenges and Future Perspective. Advancements Bioequiv Availab.
1(4). ABB.000518.2018.
Volume - 1 Issue - 4
damage of healthy cells compared to the conventional anticancer
drugs. Thirdly, synthesis of siRNA is easy and low cost as compared
to other proteins or antibiotics [4]. Besides the sequence can be
highly specific for their target organ of interest.
Clinical Trials with siRNA for Cancer Therapy
Mutations in proto-oncogene or in tumor suppressor gene lead
to cancer. This ontogenesis is potential target for gene silencing
by RNA interference mechanism. siRNA based therapy has been
used in many cancers like thyroid, prostatic, pancreatic, lung,
liver, colon, renal, non-Hodgkin lymphoma and breast cancer [5].
Alnylam Pharmaceuticals has completed phase 1 extension study
with lipid nano-particle (molecule named ALN-VSP)[6] that targets
two gens VEGF and KSP that are responsible for primary liver
cancer. Another pharmaceutical company is conducting human
phase1 study with siRNA with lipoplex delivery system (Atu-027)
[7] that targets PKN3 gene responsible for cancer metastasis that
may have potential role in advanced solid tumor. Santaris Pharma
has completed a phase II trial with siRNA-based therapy (molecule
named SPC2996)that targets BCL-2 gene responsible for chronic
lymphocytic leukemia.
Barriers of SiRNA Delivery and Future Perspective
There are still some disadvantages which restricts the clinical
trials of siRNA delivery for cancer therapy.
A. siRNA molecules are large molecule (13kDA) and
negatively charged and hydrophilic [3] and hence cannot
diffuse cell membrane alone.
B. Stability of siRNA is another important issue for siRNA. It
is easily degraded in the physiological condition by the nuclease
enzyme plasma and tissue. Half-life of unmodified siRNA [8]
in serum ranges from few minutes to 1hr. kidney is another
barrier that plays an important role in clearing the siRNA from
the body. Apart from kidney and nuclease, siRNA is taken up by
reticuloendothelial system with the help phagocytic cells [9],
including circulating monocytes and tissue macrophages.
C. Another problem of siRNA is off targeting [9] that can lead
to the silencing of gene expression of non-pathogenic genes
which, in results hinder the cellular normal function.
D. Activationofimmuneresponse[10]byhighlevelsofsiRNA
is another important challenge that restricts its therapeutic
efficacy.
E. To overcome the barriers, siRNA therapy requires suitable
drug delivery system that requires a carrier to deliver siRNA
to its targeted place. The carrier should be biologically inert,
non-immunogenic, and able to evade RE phagocytosis, prevent
renal clearance, facilitate cell entry to RNAi mechanism and
most importantly have low toxicity. Currently researches on
liposomal and various nanoparticle-based siRNA delivery
systems are underway.
Conclusion
siRNA based treatment holds a promising future in treatment of
various cancers of our body. Delivery of siRNA to its main concern is
the area of interest in research of biotechnology [11]. Various nano-
particles based and liposomal delivery systems are being tried in
various clinical studies. It can be a safe, non-toxic treatment option
compared to conventional therapies in cancer treatment.
References
1. http://www.who.int/en/news-room/fact-sheets/detail/cancer
2. Mansoori B, SandoghchianShotorbani S, Baradaran B (2014) RNA
Interference and its role in cancer therapy. Adv Pharm Bull4(4): 313-
321.
3. Xu C, Wang J (2015) Delivery systems for siRNA drug development in
cancer therapy. Asian Journal of Pharmaceutical Sciences 10(1): 1-12.
4. ChouguleMB,TekadeRK(2012)Currentsceneandprospectivepotentials
of siRNA in cancer therapy. J Pharmacogenomics Pharmacoproteomics
3: e125.
5. Chakraborty C, Sharma AR, Sharma G, Doss CGP, Lee SS (2017)
Therapeutic miRNA and siRNA: moving from bench to clinic as next
generation medicine. Mol Ther Nucleic Acids 8: 132-143.
6. Tabernero J, Shapiro GI,LoRusso PM, Cervantes A, Schwartz GK, et
al. (2013) First-in-humans trial of an RNA interference therapeutic
targeting VEGF and KSP in cancer patients with liver involvement.
Cancer Discov 3(4): 406-417.
7. Schultheis B, Strumberg D, Santel A, Vank, C, Gebhardt F, et al. (2014)
First-in-human phase I study of the liposomal RNA interference
therapeutic Atu027 in patients with advanced solid tumors. J Clin Oncol
32(36): 4141-4148.
8. Layzer JM, McCaffrey AP, Tanner AK, Huang Z, Kay MA, et al. (2004) In
vivo activity of nuclease-resistant siRNAs. RNA 10(5): 766-771.
9. Singh A, Trivedi P, Jain NK (2018) Advances in siRNA delivery in cancer
therapy. Artif Cells Nanomed Biotechnol. 46(2): 274-283.
10. Jackson AL, Burchard J, Schelter J (2006) Widespread siRNA ‘off-target’
transcript silencing mediated by seed region sequence complementarily.
RNA 12(7): 1179-1187.
11. Marques JT, Williams BR (2005) Activation of the mammalian immune
system by siRNAs. Nat Biotechnol 23(11): 1399-1405.](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)