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Gene and cell therapy of human genetic diseases: Recent advances and future directions.

Disruptions in normal development and the emergence of health conditions often result from the malfunction of vital genes in the human body. Decades of scientific research have focused on techniques to modify or substitute defective genes with healthy alternatives, marking a new era in disease treatment, prevention and cure. Recent strides in science and technology have reshaped our understanding of disorders, medication development and treatment recommendations, with human gene and cell therapy at the forefront of this transformative shift. Its primary objective is the modification of genes o

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… Transplants from genetically matched siblings offer improved outcomes, whereas transplants from unrelated donors carry the risk of graft versus host disease and heightened susceptibility to infections due to immunosuppression. 28 While enzyme replacement therapy utilizing pegylated adenosine deaminase … European Commission approval in May 2016, with a cost exceeding enzyme replacement therapy, positions Strimvelis® as a transformative solution for ADA‐SCID, an exceptionally rare disorder. …

Advancing CRISPR genome editing into gene therapy clinical trials: progress and future prospects.

Genome editing has recently evolved from a theoretical concept to a powerful and versatile set of tools. The discovery and implementation of CRISPR-Cas9 technology have propelled the field further into a new era. This RNA-guided system allows for specific modification of target genes, offering high accuracy and efficiency. Encouraging results are being announced in clinical trials employed in conditions like sickle cell disease (SCD) and transfusion-dependent beta-thalassaemia (TDT). The path finally led the way to the recent FDA approval of the first gene therapy drug utilising the CRISPR/Cas

RNAi-Based Therapeutics and Novel RNA Bioengineering Technologies.

RNA interference (RNAi) provides researchers with a versatile means to modulate target gene expression. The major forms of RNAi molecules, genome-derived microRNAs (miRNAs) and exogenous small interfering RNAs (siRNAs), converge into RNA-induced silencing complexes to achieve posttranscriptional gene regulation. RNAi has proven to be an adaptable and powerful therapeutic strategy where advancements in chemistry and pharmaceutics continue to bring RNAi-based drugs into the clinic. With four siRNA medications already approved by the US Food and Drug Administration (FDA), several RNAi-based thera

Engineering with Biomedical Sciences Changing the Horizon of Healthcare-A Review.

In the dynamic realm of healthcare, the convergence of engineering and biomedical sciences has emerged as a pivotal frontier. In this review we go into specific areas of innovation, including medical imaging and diagnosis, developments in biomedical sensors, and drug delivery systems. Wearable biosensors, non-wearable biosensors, and biochips, which include gene chips, protein chips, and cell chips, are all included in the scope of the topic that pertains to biomedical sensors. Extensive research is conducted on drug delivery systems, spanning topics such as the integration of computer modelin

Preventive strategies for acute kidney injury in cancer patients.

Acute kidney injury (AKI) is a common complication of cancer that occurs in up to 50% of neoplastic patients during the natural history of their disease; furthermore, it has a huge impact on key outcomes such as overall prognosis, length of hospitalization and costs. AKI in cancer patients has different causes, either patient-, tumour- or treatment-related. Patient-related risk factors for AKI are the same as in the general population, whereas tumour-related risk factors are represented by compression, obstruction, direct kidney infiltration from the tumour as well by precipitation, aggregatio

Human isoprenoid synthase enzymes as therapeutic targets.

In the human body, the complex biochemical network known as the mevalonate pathway is responsible for the biosynthesis of all isoprenoids, which consists of a vast array of metabolites that are vital for proper cellular functions. Two key isoprenoids, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) are responsible for the post-translational prenylation of small GTP-binding proteins, and serve as the biosynthetic precursors to numerous other biomolecules. The down-stream metabolite of FPP and GGPP is squalene, the precursor to steroids, bile acids, lipoproteins, and vitamin

Оценка эффективности, безопасности и соблюдения оральной терапии лекарств у пациентов с повторным множественным склерозом.

Предыстория и цели: Отбор соответствующих лекарственных средств для борьбы с изменением болезней (ДМР) имеет решающее значение для оптимизации лечения и замедления развития заболеваний в условиях множественного склероза (МС). Исследования в реальном мире позволяют оценить эффективность наркотиков и их использование в обычной клинической практике. Поэтому цель этого исследования состояла в том, чтобы определить эффективность и безопасность пероральной терапии для пациентов с повторно излучающимся множественным склерозом и особенностями участия в терапии. Материалы и методы: Ретроспективное и пе

Clinical development of gene therapy: results and lessons from recent successes.

Therapeutic gene transfer holds the promise of providing lasting therapies and even cures for diseases that were previously untreatable or for which only temporary or suboptimal treatments were available. For some time, clinical gene therapy was characterized by some impressive but rare examples of successes and also several setbacks. However, effective and long-lasting treatments are now being reported from gene therapy trials at an increasing pace. Positive outcomes have been documented for a wide range of genetic diseases (including hematological, immunological, ocular, and neurodegenerativ

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… Moreover, in these trials, the direct effect of gene transfer could not be ascertained as treated patients simultaneously received enzyme replacement therapy. … The study found that although systemic detoxification and immune recovery was only partial, both patients have not required enzyme replacement therapy for more than 5 years, with observations ongoing. Again, no adverse event related to vector integration was observed. …

From Innate Immunity to Cancer Therapy: Antimicrobial Peptides as Emerging Anticancer Agents.

The potential for the use of antimicrobial peptides (AMPs) as anticancer agents has garnered much interest because of their selective cytotoxicity to tumor cells and ability to evade multidrug resistance mechanisms. AMPs are shorter cationic amphiphilic molecules, part of our innate immune system, with direct membrane-disruptive activity and immunomodulatory effects. Anticancer peptides (ACPs) can be derived from natural biophysical sources or synthetically engineered, taking advantage of the unique biophysical properties of cancer cell membranes to exert their anti-tumor activities rapidly an

From undruggable to degradable: A deep learning-enabled framework for precision orthopaedic protein degradation.

BACKGROUND/OBJECTIVE: A fundamental translational impasse in musculoskeletal disorders-from osteoarthritis to bone metastases-is the "undruggability" of critical pathological drivers sequestered within anatomically restricted and avascular skeletal niches. While Targeted Protein Degradation (TPD) offers a revolutionary event-driven modality to eradicate these refractory targets, its clinical translation to orthopaedics is severely hindered by the physicochemical incompatibility of large degraders with dense extracellular matrices and the scarcity of bone-specific E3 ligases. METHODS: In this

Генетическая основа болезни.

Генетика в той или иной степени играет определенную роль во всех заболеваниях. Изменения в нашей ДНК и различия в том, как эта ДНК функционирует (одиночка или комбинация), наряду с окружающей средой (которая включает образ жизни), способствуют болезнетворным процессам. В рамках этого обзора изучается генетическая основа человеческих заболеваний, включая однородные генетические расстройства, хромосомные диспропорции, эпигенетические, раковые и сложные расстройства, и рассматривается вопрос о том, каким образом наше понимание и технологические достижения могут быть использованы для обеспечения н

Molecular Targeting and Rational Chemotherapy in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a molecularly complex disease with multiple aberrant genetic pathways involved in its pathogenesis. Approximately one-third to one-half of patients with AML would relapse, and no standard therapy is established for relapsing and/or refractory AML (RR-AML) yet. It is unlikely that blockage of only one specific pathway will lead to prolonged remissions and cures in all fractions of the AML patients population. Nowadays, novel therapeutic agents with rational combination are being recognized which improve the cure rate for relapsed AML. These drugs and their metabo

Polybasic nanogels for intracellular co-delivery of paclitaxel and carboplatin: a novel approach to ovarian cancer therapy.

Ovarian cancer is one of the leading causes of cancer-related deaths in women, with limited progress in treatments despite decades of research. Common treatment protocols rely on surgical removal of tumors and chemotherapy drugs, such as paclitaxel and carboplatin, which are capable of reaching cancer cells throughout the body. However, the effectiveness of these drugs is often limited due to toxic reactions in patients, nonspecific drug distribution affecting healthy cells, and the development of treatment resistance. In this study, we introduce a polybasic nanogel system composed of poly(die

Гут Микробиота Нарушение гематологовой терапии рака: Молекулярное понимание и последствия для эффективности лечения.

Гематологическая магнелезность (ГМ), включая лейкемию, лимфому и множественные миеломы, связана с бесконтрольным распространением аномальных кровеносных клеток, что создает серьезные клинические проблемы из-за их неоднородности и различных методов лечения. Несмотря на недавние достижения в области лечения, благодаря которым повысились показатели выживаемости, особенно в случае хронической лимфоцитической лейкемии и острой лимфоболической лейкемии, такие методы лечения, как химиотерапия и трансплантация стволовых клеток, часто нарушают микробиоту, что может негативно сказаться на результатах ле

Current evidence for the treatment of hypothyroidism with levothyroxine/levotriiodothyronine combination therapy versus levothyroxine monotherapy.

ObjectiveHypothyroidism is relatively common, occurring in approximately 5% of the general US population aged ≥12 years. Levothyroxine (LT4) monotherapy is the standard of care. Approximately, 5%-10% of patients who normalise thyroid-stimulating hormone levels with LT4 monotherapy may have persistent symptoms that patients and clinicians may attribute to hypothyroidism. A long-standing debate in the literature is whether addition of levotriiodothyronine (LT3) to LT4 will ameliorate lingering symptoms. Here, we explore the evidence for and against LT4/LT3 combination therapy as the optimal appr

Gene editing and CRISPR in the clinic: current and future perspectives.

Genome editing technologies, particularly those based on zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR (clustered regularly interspaced short palindromic repeat DNA sequences)/Cas9 are rapidly progressing into clinical trials. Most clinical use of CRISPR to date has focused on ex vivo gene editing of cells followed by their re-introduction back into the patient. The ex vivo editing approach is highly effective for many disease states, including cancers and sickle cell disease, but ideally genome editing would also be applied to diseases whic

Coexistence of Autoantibodies against the Golgi Complex and Ro52 Antigen in a Patient with Nonspecific Interstitial Pneumonia.

Nonspecific interstitial pneumonia (NSIP) is often associated with connective tissue diseases (CTD). The diagnosis of NSIP was confirmed in a 63-year-old man by high-resolution computed tomography and an open lung biopsy. Anti-Golgi complex autoantibodies (AGA) and anti-Ro52 antibodies were simultaneously detected at high concentrations. Autoantibodies to aminoacyl-tRNA synthetases (ARS) were negative. The patient was treated with corticosteroids for six months. During the seven-year follow-up, NSIP had a slow progression and patient had not developed the clinical features of CTD. The present

Insights into Facilitated Subcutaneous Immunoglobulin Use in Patients with Secondary Immunodeficiency Diseases: A FIGARO Subgroup Analysis.

The Facilitated Immunoglobulin Administration Registry And Outcomes (FIGARO) Study was a European, multicenter, prospective, observational study conducted across Europe designed to provide insights on the clinical use and tolerability of facilitated subcutaneous immunoglobulin (fSCIG). Data herein are reported for the cohort of patients with secondary immunodeficiency (SID), with a subgroup analysis by age. The SID cohort included 31 patients: 1 pediatric, 15 adult, and 15 older adult patients. Over the 36-month observation period, the median monthly dose of fSCIG (30 g) and median monthly inf

Hypophosphatasia: Results of a Country-Wide Selective Screening Program Using NGS Technology as a First-Tier Test.

Hypophosphatasia (HPP) is a rare hereditary metabolic disorder caused by nucleotide variants (NVs) in the ALPL gene, leading to a deficiency of tissue-nonspecific alkaline phosphatase (TNSALP). HPP has a variable clinical presentation (such as impaired mineralization of bones and teeth, respiratory dysfunctions, muscle weakness, muscle and bone pain, growth deficiency, nephrocalcinosis, seizures, encephalopathy, intracranial hypertension, and intellectual disability) overlapping with other disorders which often delays a correct diagnosis. In this study, we present the results of a two-center (

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… Hitherto, HPP therapy is based on enzyme replacement therapy (ERT) with recombinant TNSALP, Asfotase Alfa (Strensiq) [ 10 ]. … replacement therapy HPP | Hypophosphatasia LP | likely pathogenic NS | newborn screening NGS | next-generation sequencing NVs | nucleotide variants P | Pathogenic SNPs | Single-nucleotide polymorphisms TNSALP | Tissue-nonspecific alkaline phosphatase VUS | Variant of uncertain significance Supplementary …

PD-1 Pathway Inhibitors: Immuno-Oncology Agents for Restoring Antitumor Immune Responses.

Immune checkpoint inhibitors are designed to restore a patient's own antitumor immune response that has been suppressed during tumor development. The first monoclonal antibodies against the immune checkpoint programmed death 1 (PD-1) receptor, nivolumab and pembrolizumab, are now approved for clinical use. Both agents are indicated for the treatment of advanced melanoma, as well as for the treatment of metastatic non-small cell lung cancer (NSCLC). Nivolumab is also approved for the treatment of advanced renal cell carcinoma. In patients with melanoma, these agents result in objective response