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On August 20th, 1989, Lyle and Erik Menendez shot and killed their own parents. Until then, this Beverly Hills family had been a portrait of the American Dream. How did it go so wrong? To listen to all four episodes of 'The Menendez Brothers' right now and ad-free, go to IntoHistory.com . Subscribers enjoy uninterrupted listening, early releases, bonus content and more, only available at IntoHistory.com . If you or someone you know is in crisis, there is free help available at mhanational.org Learn more about your ad choices. Visit megaphone.fm/adchoices…
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Oncolytic Virus Construction Adenovirus has been explored and engineered extensively as an oncolytic virus and viral vector for gene therapy to reduce viral virulence and increase efficacy and specificity. E1A gene in adenovirus is responsible for viral replication in tumor cells and needs to be attenuated for oncolytic purpose. Coated protein modification is to increase target specificity of adenovirus to tumor cells, and thus alters viral tropism. Adenovirus can also be modified through transcriptional targeting, such as placing E1A and E1B gene under control of promoter of cyclooxygenase-2 enzyme (highly expressed in a range of cancers), or through post-transcriptional modification, such as targeting of cancer specific miRNA. fLHg9IQl8CS5qY7vPwjA…
Oncolytic Virus in vitro Validation Study Oncolytic virus is engineered by homologous recombination from parental virus. The recombination rate is low and parental virus has growth superiority. In order to get purified engineered oncolytic virus, several rounds of plaque purification must be performed. Scientist in Creative Biolabs has developed optimal method to do the plaque purification assay for oncolytic virus engineering.…
Oncolytic Virus Basis The strategy implementation of immunotherapeutic for the treatment of cancer has gained prominence over the past decade in preclinical development and clinical practice. Traditional oncological treatments, including surgery, radiation, and chemotherapy, aim to directly remove or kill cancer cells, but receive high probability of recurrences or serious side effects. In contrast, immunotherapy seeks to enhance the host immune system's ability to eliminate cancer cells, contributing to tumor regression, antitumor immune memory formation, and ultimately durable responses.…
Oncolytic Virotherapy Development for Combination Therapy with Cancer Vaccines Oncolytic virotherapy (OV) represents an exciting new area of cancer treatment by exploiting a virus's ability to selectively replicate and kill tumor tissue while stimulating a patient-specific immune response against cancer.…
Cytokine/Chemokine-expressing Oncolytic Virus Genetic therapies, such as transfected viral vectors and immune cells, continue to display clinical responses as systemically deliverable and targeted therapeutics, with the first such strategy having been approved for cancer treatment. Most of these use cytokine transgenes.…
Antitumor effect of oncolytic virus The antitumor effect of oncolytic virus can be analyzed by calculating the tumor size, tumor weight or through in vivo imaging, such as bioluminescence imaging (BLI) and position emission tomography (PET).
Example 1: CCL5 Expressing Oncolytic Virus The chemokine CCL5 is a RANTES, which is able to regulate upon activation and normal T cell expressed. It plays an important part in several human diseases and binds to three receptors: CCR1, CCR3, and CCR514, which are expressed on a variety of types of effector and regulatory T cells. It is formed by both activated T lymphocytes and antigen presenting cells, and is widely chemoattractive. Recently, researchers have demonstrated that vvCCL5 (an oncolytic vaccinia virus expressing CCL5) constitutively expressing CCL5, promotes immune infiltration of mouse colorectal tumors in vivo and improves therapeutic effects. Besides, CCL5 expression also induces prolonged persistence of the virus exclusively within the tumor. What's more, further improvement of antitumor effectiveness is observed when vvCCL5 is used together with type-1-polarized dendritic cells (DC1) vaccination, along with enhanced immune cell infiltration into the tumor and an obvious T1 skewing of the infiltrating T-cells.…
Plaque Purification Assay Oncolytic virus is engineered by homologous recombination from parental virus. The recombination rate is low and parental virus has growth superiority. In order to get purified engineered oncolytic virus, several rounds of plaque purification must be performed. Scientist in Creative Biolabs has developed optimal method to do the plaque purification assay for oncolytic virus engineering.…
Combination Therapy of Oncolytic Virus with Conventional Radiotherapy Nowadays, overcoming malignant tumors is still a major research topic in the medical community. The current methods of treating tumors are mainly surgery, chemotherapy and radiotherapy. Radiosensitivity is the key to determine the success or failure of tumor radiotherapy. Finding ways to improve tumor radiosensitivity has become a research hotspot in the field of tumor therapy. Oncolytic virus therapy is a new tumor gene therapy approach that has emerged in recent years. This therapy uses genetic engineering methods to transform the virus so that the virus can selectively replicate in the tumor and produce oncolytic effects. There is no cross-tolerance between oncolytic virus therapy and traditional radiotherapy. The combined application of the two methods can achieve superposition or synergy.…
With the significant progressing of scientific research and numerous ongoing pre-clinical development, messenger RNA has become a promising therapeutics modality for various indications including cancers and infectious diseases. https://mrna.creative-biolabs.com/
tRNA with s²U modifications shows a more stable structure and resistance against extreme thermophiles. Lack of the s²U modifications will result in growth defects, sensitivity to high temperatures, even protein misfolding in bacteria. Abnormality of s²U modification in humans is implicated with acute infantile liver failure and other dysfunctions. https://mrna.creative-biolabs.com/2-thiouridine.htm…
5-Methylcytidine (m⁵C), also called 5-methyl-cytidine, is a modified nucleoside derived from 5-methylcytosine (5mC), in which a methyl group is linked to the C-5 in the 6-atom ring of cytosine base catalyzed by DNA methyltransferase. 5mC has been considered to be the fifth DNA base, which is common in DNA deoxynucleotides of many animals and plants, also is found in ribonucleic acids of animal, plant, and bacterial organisms. In animals, especially vertebrates and mammalian, 5mC is mainly present in cytosine-guanine sequence (CpG), while, 5mC can be found in multiple sites and served as a marker to protect DNA from being cut by the methylation-sensitive restriction endonuclease. In vitro, 5mC can be derivatives into 5-hydroxymethylcytosine and thymine under corresponding reaction conditions. https://mrna.creative-biolabs.com/5-methylcytidine.htm…
The classical cap structure is a 7-methylguanosine moiety connected to the mRNA via a triphosphate linkage at 5'-end (m7GpppG or m7G). It can be recognized by several specialized proteins involved in mRNA transport, translation, translational repression and degradation. 6-thioguanosine (s6G) is a photosensitive molecule that can photo-crosslink to both proteins and nucleic acids to study cap-protein and cap-nucleic acid interactions at the molecular level.https://mrna.creative-biolabs.com/6-thioguanosine-containing-cap.htm…
Methods of mRNA stability tests such as transcription inhibition initially are proved most amenable for high-throughput technologies. Actinomycin D is a fast-acting DNA intercalator which is widely used as a transcription inhibitor to achieve mRNA inhibition in mRNA stability assays. The level of an mRNA transcript could be quantified to measure the half-life of specific mRNAs either when the mRNA is in a steady-state or after the inhibition of mRNA synthesis by actinomycin D. https://mrna.creative-biolabs.com/actinomycin-d-based-method.htm…
Actinomycin D-based method as an easy approach has several advantages, for example, it does not require the construction and introduction of exogenous genes into cells. Although this method does not permit quantitative estimates of mRNA stability, it allows the easy analysis of mutant genes and thus may be useful for measuring the mRNA stability mechanism. Moreover, actinomycin D-based methods can determine the abundance of mRNA sequences following transcription inhibition, which allows the assessment of mRNA decay and stability. https://mrna.creative-biolabs.com/actinomycin-d-based-method.htm…
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