See how gene therapy uses vectors, or delivery systems, in order to introduce genetic material to target cells.
Category: biotech/medical – Page 96
Emerging non-viral vectors for gene delivery
The development of COVID-19 vaccines has sparked widespread interest. mRNA-based therapies are rapidly gaining attention owing to their unique advantages in quickly developing vaccines and immunotherapy for various ailments [1, 2]. Given that most human diseases stem from genetic factors, gene therapy represents a promising modality for addressing various inherited or acquired disorders by replacing faulty genes or silencing genes [3]. Gene therapy encompasses the targeted exploitation of genetic material, which includes gene replacement through DNA or mRNA [4, 5]; gene silencing utilizing siRNA or miRNA [6], and CRISPR-Cas9 based gene editing [7].
However, achieving safe and efficient gene delivery to specific cells requires overcoming multiple biological barriers, including extracellular obstacles such as enzyme degradation, serum protein interactions, electrostatic repulsion of genes and cell membranes, and innate immune system, as well as intracellular obstacles such as endosomal escape, transport barriers, precise release [8]. Therefore, gene vectors require several characteristics such as high gene condensation; favorable serum stability to avoid non-specific serum protein interactions, endonuclease degradation, and renal clearance; achieved specific targeting cell or tissues; effective transport into the cytoplasm thereby facilitating gene transfection (mRNA, siRNA and miRNA); precise gene release and scheduling, and nuclear localization that enables DNA transcription. Comprehensive exploration of transfection mechanisms can aid in the development of high-performance gene vectors [9, 10].
Gene vectors generally include viral vectors and non-viral vectors. Presently, approximately 70% of clinical gene therapy trials employ viral vectors, which include retroviruses, lentiviruses, adenoviruses, and adeno-associated viruses. Due to their exceptional infectivity, virus-based vectors typically exhibit excellent gene transfection capabilities. However, the clinical safety of viral vectors has been questioned due to their propensity to stimulate immunogenic reactions and induce transgene insertion mutations. Moreover, viral vectors possess several limitations, including low gene loading capacity, inability to deliver large-sized genes, complicated preparation procedures, and the patient cannot be repeatedly administered [4]. In contrast, non-viral vectors, particularly lipid nanoparticles (LNPs) and cationic polymers, have demonstrated robust gene loading capacity, heigh safety and practicability, simplicity preparation [10, 11]. Consequently, non-viral vectors are exhibiting tremendous potential for further clinical development and application. Our review primarily highlights the significant potential of non-viral vectors, particularly lipid nanoparticles (LNPs), highly branched poly(β-amino ester) (HPAE), single-chain cyclic polymer (SCKP), poly(amidoamine) (PAMAM) dendrimers, and polyethyleneimine (PEI). We intend to provide a detailed examination of the latest research progress and existing limitations of non-viral gene vectors over recent years.
Functional Biomaterials for Drug Delivery
Gene therapy is a technique that rectifies defective or abnormal genes by introducing exogenous genes into target cells to cure the disease. Although gene therapy has gained some accomplishment for the diagnosis and therapy of inherited or acquired cardiovascular diseases, how to efficiently and specifically deliver targeted genes to the lesion sites without being cleared by the blood system remains challenging. Based on nanotechnology development, the non-viral vectors provide a promising strategy for overcoming the difficulties in gene therapy. At present, according to the physicochemical properties, nanotechnology-based non-viral vectors include polymers, liposomes, lipid nanoparticles, and inorganic nanoparticles. Non-viral vectors have an advantage in safety, efficiency, and easy production, possessing potential clinical application value when compared with viral vectors. Therefore, we summarized recent research progress of gene therapy for cardiovascular diseases based on commonly used non-viral vectors, hopefully providing guidance and orientation for future relevant research.
Cardiovascular disease (CVD) leads to almost a third of all deaths worldwide, resulting from atherosclerotic plaque leading to hemadostenosis and blood flow restriction (Park et al., 2020; Tsao et al., 2022). Despite progress in medical technology, CVD is still a major cause of death (Yang et al., 2023). Conventional treatment strategies for CVD include anticoagulation, antiplatelet, thrombolytics, hypolipidemic drugs, and invasive therapies like vascular bypass grafting and stent transplantation (Zhu et al., 2021). However, small molecule drug therapy in conventional treatment strategies is characterized by short half-life and low bioavailability, and long-term use of certain drugs may also lead to side effects such as drug resistance and potential hematological toxicity (Missri, 1979; Fu et al., 2014). Surgical treatment, on the other hand, is more pro-traumatic, requires a longer recovery time, and has a high risk of postoperative complications.
Brain structure changes in people who work long hours
If you need an excuse to turn off the laptop over the weekend or rein in overtime, scientists have found that working extended hours actually changes parts of the brain linked to emotional regulation, working memory and solving problems. While we know the toll that “overwork” takes physically and mentally, the precise neurological impact has not been well understood.
An international team of researchers including scientists from Korea’s Chung-Ang University assessed 110 healthcare workers – 32 who worked excessive hours (52 or more per week) and 78 who clocked less than 52 hours per week, or what would be considered closer to standard hours in the field. Voxel based morphometry (VBM) to assess gray matter and atlas-based analysis was then applied to MRI scans of each individual’s brain, identifying volume and connectivity differences.
When the scientists adjusted the results to account for age and sex, they found that, in the overworked cohort, the imaging showed a significant difference in brain volume in 17 different regions of the organ – including the middle frontal gyrus (MFG), insula and superior temporal gyrus (STG). Atlas-based analysis identified that, in the overworked individuals, there was 19% more volume in the left caudal MFG. The MFG – part of the brain’s frontal lobe – is the heavy lifter when it comes to executive functioning like emotional regulation, working memory, attention and planning, while the STG’s main task is auditory and language processing. The insula, meanwhile, is key in pain processing and other sensory signaling.
Better than stitches: Researchers develop biocompatible patch for soft organ injuries
University of California, Los Angeles and University of California, San Diego researchers developed an injectable sealant for rapid hemostasis and tissue adhesion in soft, elastic organs.
Formulated with methacryloyl-modified human recombinant tropoelastin (MeTro) and Laponite silicate nanoplatelets (SNs), the engineered hydrogel demonstrated substantial improvements in tissue adhesion strength and hemostatic efficacy in preclinical models involving lung and arterial injuries.
Injuries to soft tissues such as lungs, heart, and blood vessels complicate surgical closure due to their constant motion and elasticity. Sutures, wires, and staples are mechanically fixed, risking blood loss when applied to tissues that expand and contract with each breath or heartbeat. Existing hemostatic agents, including fibrin-based sealants, aim to stem blood flow but may trigger intense coagulation responses in patients with clotting disorders.
Psychological treatment linked to physical brain changes that ease chronic pain
Back pain, migraines, arthritis, long-term concussion symptoms, complications following cancer treatment—these are just a few of the conditions linked to chronic pain, which affects 1 in 5 adults and for which medication is not always the answer.
Now, a new review study offers insight into how specific types of psychological treatment can help relieve this pain through physical changes in the brain.
The research article was published today in The Lancet. The study was led by Professor Lene Vase from the Department of Psychology at Aarhus BSS, Aarhus University.
GPS for proteins: Tracking the motions of cell receptors
Taste, pain, or response to stress—nearly all essential functions in the human body are regulated by molecular switches called G protein-coupled receptors (GPCRs). Researchers at the University of Basel have uncovered the fundamental mechanism for how such a GPCR works.
Using a method similar to the Earth satellite GPS, they could track the motions of a GPCR and observe it in action. Their findings, recently published in Science, provide guidance for designing drugs.
GPCRs are embedded in the cell membrane and transmit signals from the outside to the inside of the cell. Because of their vast diversity and crucial role in the body, GPCRs are targeted by many drugs, such as painkillers, heart medications, and even the semaglutide injection for diabetes and obesity. In fact, about one-third of all approved drugs target GPCRs.