This research project will aim to explore antisense-based therapeutics in two key areas, it’s therapeutic potential and it’s utility as a research tool. Antisense technology uses a single stranded molecule that is complementary to a specific sequence and binds to that sequence to ultimately silence it. With two antisense based therapies being approved by the FDA, antisense based therapeutics have been shown to hold potential in both research development and therapeutics. A literature search will be undertaken comprising of books, journals, review articles, news articles and clinical trials. The evidence will then be categorised against the aims of the project. The evidence will be assimilated through critical analysis using research methodology assessing the quality of research papers and systematic reviews using tools such as PRISMA. A descriptive summary and tables will be used to present the evidence using objective statistical tools where possible and meta-analysis will be applied if the data is homogeneous. The project aims to critically evaluate the available evidence highlighting the therapeutic potential of antisense treatments in specific disease areas as well as its future potential. The research potential of antisense as a tool will also be evaluated using an evidence based approach. Background Antisense-based therapeutics have attracted much interest as a novel class of agents for the treatment of ‘viral infections, cancers and genetic disorders due to their
Evaluating the eight papers for quality evidence was critical when selecting the two papers to utilise. The evidence hierarchy was considered, aiming to use the highest evidence possible, such as systematic reviews and meta-analyses; and randomized, controlled, double-blind studies, to ensure the most accurate evidence informed the clinical decision for the patient (Bloom, Olinzock, Radjenoic & Trice, 2013). When sorting the results, other various factors were also taken into consideration; credibility, reputability, reasonability and support. With these factors taken into account, the two papers selected are highly esteemed in regards to evidence, and are most relevant to the patient (Stichler, 2010).
--why might the developers have chosen this backbone over other possibilities for antisense or siRNA molecules? (5%)
Since the arrival of triple therapy, the challenge of sustained and complete viral suppression has been solved for the majority of patients [1]. The major limiting factors for improving the long-term success of ART are tolerability and convenient pill burden [2]. The latest class of the antiretroviral drug developed are Integrase inhibitors (INI). Dolutegravir (DTG) is an Integrase inhibitor, particularly focused on maintaining a favorable safety profile and a high efficiency rate, within a single-tablet regime (STR), it improves resistance barrier and allowing co-formulation with an NRTI backbone. Dolutegravir has been compared against both other classes of HIV anti-retrovirals as well as other integrase nuclear strand inhibitors. In August 2013, DTG was approved by FDA for its use in both patients who have never taken ART (ART-naïve) and patients who have taken ART (ART-experienced) [3]. It is predicted that very soon a STR containing Dolutegravir (DTG), abacavir (ABC) and lamivudine (3TC) will become
This article covers the Seneca Valley Virus (SVV-001) as a hopeful for an oncolytic treatment of certain cancer types. More specifically those with neuroendocrine properties such as rhabdomyosarcoma, Wilms tumor, glioblastoma, neuroblastoma, and adult small-cell lung cancer. Each of which effect smooth/skeletal muscle cells, kidneys/adrenal glands (mainly in children), astrocytes of the brain, nerve cells of a fetus, and lung cells in adults respectively. The virus was discovered by accident in a contaminated cell culture that contained bovine serum to promote growth. The virus was later discovered to be almost exclusively found in farm animals such as cows and pigs, due to the presence of neutralizing antibodies that were later to only ever have been found in one human sample. Just as important as that, the virus only targets the cells of the above-mentioned cancers/tumors, is a self-replicating RNA virus, and its inability to infect other cells in the body all come together to result in the lysis of these specific cancer cells. These properties alone give great hope for SVV-001 as a treatment for those infected by these diseases, and prompted for more research into its medicinal possibilities.
Step 1: How will you identify the “vital” cellular protein that the virus targets for degradation? (Hint: think proteomics). (3 pts.)
Medique Alcalak. Medline Plus. DailyMed. U.S. National Library of Medicine. Washington, D.C. Available at: http://dailymed.nlm.nih.gov. Accessed March 6,
U.S food and drug administration (FDA) are trying to approve BENLYSTA as a treatment for autoimmune disease Lupus. BENLYSTA would become the new treatment for Lupus in 52 years. The chief Executive had issues a statement about that people are excited that they had found a new medical breakthrough to help with Lupus. The people with Lupus voices were heard loud when they heard that there was a breakthrough coming. Each person is unique, and they all hope that BENLYSTA is approved. FDA is still running testes to make sure that it’s affective to all case of Lupus.
Herpes Simplex Virus(HSV) was identified as a highly attractive candidate for oncolytic virotherapy due to several reasons including the naturally cytolytic life cycle of HSV and the ability to infect a broad range cell type, a highly prevalent human pathogen which in vast majority of cases causes a self-limiting disease that can be treated with antivirals in life threatening cases and so on. The initial focus of oncolytic HSV (oHSV) virotherapy involved demonstrating the safety of oHSVs for the treatment of cancer.
A protease inhibitor is therefore a drug used to interfere with the key stage of viral replication and used to stop this fatal process.
In July, 2006, FDA approved the drug Elaprase, before that this drug was not aloud to be sold in the United States. Now Elaprase is one of the major treatments for Hunter syndrome. This particular disease is known to be found in children 1 to 3 years of age, this disease creates a defect in the human body by not manufacturing the chemical iduronate 2 sulfatase. The human body needs this chemical to help break down the sugars made in the body. Symptoms found in having this disease could be joint stiffness, and growth delay. In severe cases one may see lung and heart problems. Elaprase was approved mainly for the fact of how much success it had on patients. After the 53 week trial of Elaprase many patients that experienced the infusions compared
Medications only work for about fifty to seventy-five percent of the people whom take it, so there is no way of knowing for sure if it will work. Luckily we are switching to a more personalized approach to medicine. We are looking at the best therapies based on genetic materials and other predictive factors. “In an era of increasingly scarce resources for health research, it is critical to ensure that outdated barriers in the regulatory system are removed and limited dollars are spent more effectively to meet the needs of patients” (NHS). We have to make sure that we are spending our money in the right places. This is why we have to continuously update our regulatory system by taking out any barriers that would affect our ability to create therapies for unmet medical needs.
It may be possible to correct an abnormality in a tumor suppressor gene such as P53 by inserting a copy of the wild-type gene; in fact, insertion of the wild-type P53 gene into P53-deficient tumor cells has been shown to result in the death of tumor cells (3). This has significant implications, since P53 alterations are the most common genetic abnormalities in human cancers. The over expression of an oncogene such as K-RAS can be blocked at the genetic level by integration of an antisense gene whose transcript binds specifically to the oncogene RNA, disabling its capacity to produce protein. Experiments in vitro and in vivo have demonstrated that when an antisense K-RAS vector is integrated into lung cancer cells that over express K-RAS their tumorigenicity is decreased (4).
An extensive literature search was conducted regarding the topic of this paper. Databases utilized were: CINAHL, MEDLINE, PubMed, EbscoHost, and Google. Inclusion criteria included English language only research articles and publication dates ranging from 2009 to 2014
Gothic Elements in The Fall of the House of Usher Gothic literature is known as writing that utilizes dark and picturesque scenery, melodramatic narrative devices, and an overall atmosphere of mystery and trepidation. Many of the components that are used throughout gothic literature are seen today in horror movies. Edgar Allan Poe acts as a very influential gothic literary writer. Poe uses all of the elements of gothic literature in the majority of his stories. In Edgar Allan Poe’s short story, The Fall of the House of Usher, elements of gothic literature are portrayed through the use of distorted characters, peculiar circumstances, and intense incidents.
This have been observed with anti EpCAM, the HER family CEA, and PSMA, while the final outcomes of clinical trials did not reach the expected levels of benefit, these show great potential, when better formats of BsAbs are designed, these can could become a very effective tool to treat this neoplasm (Yu et al., 2017).