Emergence of Adeno Associated Virus Vector in Gene Therapy

Emergence of AAV in Gene Therapy

Gene therapy has been a significant development in medicine for nearly 40 years, focusing on treating genetic disorders by injecting specific genetic material into a patient to alter cell activity and address hereditary illnesses. Four fundamental gene therapy techniques include gene silencing, gene addition, gene replacement, and gene editing. Adeno-associated viruses (AAVs) are a type of gene therapy vehicle that was initially discovered as a contaminant of adenovirus preparations. The first human gene therapy study was conducted in 1970 when American physician Stanfield Rogers tried to cure argininemia with a papillomavirus-containing arginase. The primary vector for in vivo gene therapy delivery is recombinant AAVs (rAAVs). The first rAAV gene therapy treatment, Alipogene tiparvovec (Glybera), received approval in 2012 for lipoprotein lipase deficiency. In 2017, the US FDA approved Luxturna (Voretigene Neparvovec) as the first retinal gene therapy for human use, specifically for patients with LCA type 2, an inherited retinal degeneration caused by mutations in the RPE65 gene. AveXis developed Onasemnogene abeparvovec (Zolgensma®) for spinal muscular atrophy (SMA). This blog summarises the emergence and applications of AAV in gene therapy platform.

Gadolinium based Contrast Agents (GBCAs) in Magnetic Resonance Imaging (MRI)

Gadolinium based Contrast Agents (GBCAs) in Magnetic Resonance Imaging (MRI)

Magnetic resonance imaging (MRI) is a crucial technique for disease diagnosis and treatment, with gadolinium-based contrast agents (GBCAs) being useful and safe in some cases. GBCAs are pharmaceuticals that enhance diagnostic image information by altering tissue properties, influencing contrast mechanisms. They are used in MRI to study proton (1H) relaxation processes in water and soft tissues in biological systems. GBCAs are administered intravenously and distributed throughout the body, with most being eliminated within hours. They shorten the T1 and T2 relaxation times of water molecules, resulting in brighter signals on T1-weighted images and darker signals on T2-weighted images. When administered at relatively low doses in individuals with normal renal function, all GBCAs approved for clinical use have a broad safety margin. Understanding an agent’s relaxivity, concentration, and chelate stability is important for radiologists as these properties impact patient safety and the effectiveness of diagnosis. This blog summarizes an overview of Gadolinium based contrast agents usage in the diagnostic MRI imaging.

Therapeutic Modalities for Spinal Muscular Atrophy (SMA)

Spinal Muscular Atrophy (SMA) is a genetic disorder causing muscle weakness and atrophy due to the degeneration of alpha motor neurons in the spinal cord. SMA is a major cause of hereditary mortality globally, with carriers estimated to be 1/40–1/60. Assistive equipment include, adaptive strollers, wheelchairs, and support devices. Target therapies like Nusinersen, Risidiplam, and Onasemnogene abeparvovec target the underlying disease mechanism and may prevent or slow SMA progression. Risdiplam compensates for the loss of SMN2 function in SMA patients, while Onasemnogene abeparvovec is a gene therapy that delivers a functional copy of the human survival motor neuron gene to patients, showing significant improvement in developmental motor milestones. Nusinersen is an antisense oligonucleotide (ASO) used to treat 5q Spinal Muscular Atrophy (5q SMA). It alters SMN2 gene splicing to increase SMN protein synthesis, correcting the disease’s underlying cause. Nusinersen helps produce full-length (100%) SMN protein essential for motor neuron function. Palliative, supportive, and rehabilitative treatment for SMA includes orthopaedic care, dietary assistance, end-of-life care, and pulmonary management, with severity varying based on disease type. The numerous therapy approaches to treat and assist people with SMA are the main topic of this blog.

Role of Ferroptosis – A Novel Programmed Cell Death in Temozolomide Therapy for Brain Cancer

TEMOZOLOMIDE- Role of Ferroptosis in Brain Cancer

Glioblastoma (GBM) are the most prevalent type of primary malignant brain tumor in adults that can develop in the brain stem, cerebellum, or spinal cord. Temozolomide (TMZ) is an alkylating agent that is used to treat adults with newly diagnosed GBM and resistant anaplastic astrocytoma who have progressed on a nitrosourea and procarbazine-containing therapy regimen. Ferroptosis, a novel form of programmed cell death, plays a crucial role in glioblastoma therapy. Cell membrane damage produced by mechanisms such as intracellular iron build-up, reactive oxygen species (ROS), lipid peroxidation, glutathione peroxidase (GPX) activity failure, and x-catenin (xCT) causes ferroptosis (iron dependent programmed cell death). This blog discusses the molecular mechanisms of ferroptosis, its application, and challenges in the development and treatment of glioblastoma. GBM invasiveness and treatment resistance may increase if ferroptosis is avoided due to changes in glucose, lipid, glutamine, and iron metabolism. Targeting ferroptosis, which involves fatal phospholipid peroxidation due to dysregulated redox homeostasis and cellular metabolism, could be a promising treatment for GBM, as it is essential for tumor cell viability.

Artificial Intelligence (AI) making strides in Electrocardiography (ECG)


Cardiovascular disease continues to be a major concern, and the electrocardiogram (ECG) is a proven non-invasive technique for detecting cardiac issues. Traditional diagnosis, on the other hand, is based on an individual patient’s medical history and clinical examinations, which are ineffective owing to diverse data. By analyzing the electrical activity of the heart, AI is being used to identify prognostic arrhythmias such as atrial fibrillation. Deep convolutional neural networks (CNNs) are the basic building blocks of machine learning algorithms used in cardiovascular medicine to analyze ECG data. The adoption and use of AI-based diagnostic tools in clinical settings, however, may be limited by issues with interpretability and openness, such as evaluating models’ performance across datasets, processing power consumption, privacy and security concerns, imbalanced and limited datasets, and lack of clear guidelines for CNNs. Nevertheless, these technologies offer standardization, continuous, real-time monitoring, and more accurate interpretation—all of which have the potential to improve patient outcomes. This blog provides an overview of AI technologies applied and the challenges associated with the ECG in the diagnosis of cardiovascular diseases.

PERTUZUMAB Advancing in HER2-Positive Breast Cancer


Breast cancer is a diverse disease with varying clinical presentations, morphologic features, and molecular characteristics. It is influenced by various genetic pathways and is a major trend in breast cancer care. Neoadjuvant chemotherapy is a major trend, requiring integrated multidisciplinary care from pathologists, radiologists, surgeons, and oncologists. Anti-HER2 therapy has improved clinical results for HER2-positive breast cancer patients.

Pertuzumab, a humanized monoclonal antibody, targets the extracellular dimerization domain of HER2, inhibiting downstream signaling and cell survival pathways. It is used in conjunction with trastuzumab and docetaxel to treat HER2-positive metastatic breast cancer. In addition to directly encouraging the death of cancer cells, monoclonal antibodies also trigger immunological activation, which is deadly to tumour cells.

Pertuzumab possesses the capability to elicit immune effector responses, including cell-mediated cytotoxicity that is dependent on antibodies. The antibody targets the PI3K/AKT and RAS/MEK/ERK pathways, protecting normal cells from suicide. It can activate immunological effector mechanisms, such as antibody-dependent cell-mediated cytotoxicity. Trastuzumab and pertuzumab function in complementary ways, highlighting the importance of understanding the biology of this devastating disease. This blog focuses on the mechanism of pertuzumab in patients with early-stage HER2-positive breast cancer receiving neoadjuvant treatment.

Gene Therapy Perspective of Autosomal Recessive & Dominant Disorders

Gene Therapy Perspective of Autosomal Recessive & Dominant Disorders

In this blog, our focus would be on autosomal dominant disorders and autosomal recessive disorders that can be cured with a gene therapy approach. Gene therapy has faced numerous obstacles and it took an extensive period of time for reaching up to the clinic from the research lab. However, continuous and rapid advancement in the molecular biology and genomics field set the stage to develop gene therapies for a range of inherited disorders. Because of the certain limitation of the application of drug and surgical treatment, some of the cardiovascular disease also needed gene therapy approaches. Though huge progress has been observed in the treatment of autosomal recessive disorders by delivering the normal exogenous genes that can restore the proper biological function of the affected or mutated gene. However, a similar outcome cannot be expected in the case of autosomal dominant disorder as precise differentiation is required between diseases/mutated alleles from that of healthy/unaffected alleles.

Current Scenario of Clinical Trials of Cell, Gene and RNA Therapies

Current Scenario of Clinical Trials of Cell, Gene and RNA Therapies

Constant emergence of new gene therapies as well as refinement of the existing ones changes the global landscape of the cell and gene therapies clinical trials, where the US, China, and Europe are leading in respect of the number of trials conducted. As per Global Data, China showed 15% faster growth in cell and gene therapy clinical trials making the Asia-Pacific region contributes for one-third of the trial activities. As a result, the Asia Pacific region is witnessing 50% faster growth than the rest of the world (ROW). Asia Pacific region leads globally in terms of CAR-T cell gene therapy clinical trials for the time period 2015-2022 since China alone conducted ~60% of all CAR-T trials. Till April 2022, there are 19 approved gene therapies, 17 RNA-approved therapies while 56 non-genetically modified approved cell therapies (Figure 1). Details of the approved location of the clinical trials of gene therapies and RNA therapies drug product are provided in Table No.1 and Table No. 2 respectively, which presents a bird’s-eye view of the landscape of the clinical trials of the approved gene and RNA therapies.

Insectome: A treasure trove of pharmaceutical compounds

Quite often we hear people talking about microbiome disturbance leading to unhealthy aging and going back to our ancestral habits including paleo diet has the potential to cure many diseases. This folk wisdom is supported by some recent scientific publications. However, we have majorly neglected the fact that paleo diet-eating and cave-dwelling ancestors of ours had several insects on their bodies, and inside caves, they constantly fought with insects. Thus we argue, if modern habits are responsible for the current epidemic of metabolic/cardiovascular/neurological and other degenerative diseases, may be insects also had some role to play in the healthier aging of our ancestors as compared to us. In this blog post, we would like to review the benefits of insect bitings/stings published in the literature. Thus we will examine, if an apparent parasitic interaction between humans and insects is a mutualistic relationship in disguise. When an insect bites/stings us, it releases a barrage of biologically active compounds, including those with potential to act as anticoagulant/vasodilator. Can these chemicals be exploited to cure Cardio-Vascular-Diseases/dissolve internal blood clots? More importantly, there are other chemicals which have virucidal, anti-cancer and antimicrobial properties, which in either native or modified form can be repurposed for pharmaceutical applications.

Engineered Nanoparticles for the Delivery of Anticancer Therapeutics

Engineered Nanoparticles for the Delivery of Anticancer Therapeutics

Therapeutic agents in cancer treatment are aimed at rapidly dividing cells, limiting their multiplication, and promoting apoptosis. The lack of selectivity of these conventional methods resulted in needless damage to normal cells leading to severe adverse effects. Nanotechnology in medicine gratifies the constraint in conventional treatment by delivering conventional drugs to the targeted tissue or organ and plays an important role in targeting the delivery, thereby avoiding systemic toxicity and increasing the bioavailability and therapeutic index of the drug. The advantage of using nanoparticles as drug carriers are in their binding competence and reversing multidrug resistance. Using active and passive targeting strategies, nanoparticles enhance intracellular drug concentrations. The present review focuses the on the basic pathophysiology of cancer and the various types of nanoparticulate drug delivery systems that have been explored so far, taking advantage of the tumor vasculature and other molecular mechanisms which differentiates cancer cells from normal ones, for the delivery of anticancer therapeutics for effective management of cancer. The article also aims to focus on the various surface-engineered nanoparticles for the targeted delivery of cancer.