ABSTRACT
Approximately 90% of malignancies have been shown to have human telomerase activity, establishing it as a viable therapeutic target. The crystal structure of telomerase was determined recently. However, the tertiary structure of the non-conserved flexible linker region remains unresolved. This study aims to predict the full-length tertiary structure of the human telomerase reverse transcriptase (hTERT). Two strategies were employed to determine the full-length structure of hTERT (1132 amino acids); iterative threading and a conjoined model generated from machine learning and energy functions. After energy minimization, Ramachandran Plot analysis, and simulation; the conjoined model was considered of better quality and stability. The linker region of the conjoined depicted two helices from approximately 275-284 and 201-211 amino acids respectively in contrast to the iterative threading model which has a single helix. Moreover, the region was observed to undergo major structural changes throughout the simulation. These changes signify its flexibility which might be due to the region having a significant number of glycine and proline and could enhance the clamping movement.Communicated by Ramaswamy H. Sarma.
ABSTRACT
Cancer is one of the major causes of mortality worldwide, therefore it is considered a major health concern. Breast cancer is the most frequent type of cancer which affects women on a global scale. Various current treatment strategies have been implicated for breast cancer therapy that includes surgical removal, radiation therapy, hormonal therapy, chemotherapy, and targeted biological therapy. However, constant effort is being made to introduce novel therapies with minimal toxicity. Gene therapy is one of the promising tools, to rectify defective genes and cure various cancers. In recent years, a novel genome engineering technology, namely the clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein-9 (Cas9) has emerged as a gene-editing tool and transformed genome-editing techniques in a wide range of biological domains including human cancer research and gene therapy. This could be attributed to its versatile characteristics such as high specificity, precision, time-saving and cost-effective methodologies with minimal risk. In the present review, we highlight the role of CRISPR/Cas9 as a targeted therapy to tackle drug resistance, improve immunotherapy for breast cancer.
ABSTRACT
The COVID-19 pandemic has become a serious concern and has negatively impacted public health and the economy. It primarily targets the lungs, causing acute respiratory distress syndrome (ARDS); however, it may also lead to multiple organ failure (MOF) and enhanced mortality rates. Hence, there is an urgent need to develop potential effective therapeutic strategies for COVID-19 patients. Extracellular vesicles (EVs) are released from various types of cells that participate in intercellular communication to maintain physiological and pathological processes. EVs derived from various cellular origins have revealed suppressive effects on the cytokine storm during systemic hyper-inflammatory states of severe COVID-19, leading to enhanced alveolar fluid clearance, promoted epithelial and endothelial recovery, and cell proliferation. Being the smallest subclass of EVs, exosomes offer striking characteristics such as cell targeting, being nano-carriers for drug delivery, high biocompatibility, safety, and low-immunogenicity, thus rendering them a potential cell-free therapeutic candidate against the pathogeneses of various diseases. Due to these properties, numerous studies and clinical trials have been performed to assess their safety and therapeutic efficacy against COVID-19. Hence, in this review, we have comprehensively described current updates on progress and challenges for EVs as a potential therapeutic agent for the management of COVID-19.
