Ganesh Shankar Vidyarthi Memorial Medical College

Genome editing has revolutionized molecular biology. It offers precise modification of genetic material across diverse organisms. This review outlines the evolution of genome editing technologies from homologous recombination to advanced Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (CRISPR-9) based systems that now dominate the field. Early methods, such as Zinc Finger Nucleases (ZFNs) and Transcription Activator-Like Effector Nucleases (TALENs), established the foundation for site-specific DNA cleavage. However, they were limited by complexity and cost. The advent of the CRISPR-Cas systems, particularly CRISPR-Cas9, transformed the landscape due to their simplicity, high efficiency, and adaptability. Variants such as CRISPR-Cas12a, base editors, and prime editors enhanced editing precision. They enable single-nucleotide modifications and targeted insertions without double-strand breaks. Emerging tools such as CRISPR-associated transposases, recombinase fusions, and RNA-targeting Cas13 enzymes expand the scope of manipulation beyond DNA to RNA. At the same time, epigenome editing, and gene drives present new therapeutic and ecological applications. Efficient delivery systems, both viral (Adeno-Associated Virus (AAV), lentivirus, adenovirus) and non-viral (lipid nanoparticles, gold nanoparticles, DNA nano clews), remain critical for clinical translation. Future directions emphasize artificial intelligence-guided design, retroelement-based integration, and novel biomimetic delivery vehicles to overcome current efficiency and safety barriers. These innovations can help overcome current efficiency and safety barriers. Together, they are propelling genome editing toward precise, programmable, and ethically responsible therapeutic applications. Despite unresolved challenges involving off-target effects, immunogenicity, and germline ethics, genome editing redefines biomedical research, drug development, and disease correction. CRISPR-derived technologies now stand at the forefront of next-generation genetic medicine.

To evaluate the safety and efficacy of a fixed-dose combination (FDC) of tamsulosin prolonged release (PR) and tadalafil in moderate-severe benign prostatic hyperplasia (BPH) and erectile dysfunction (ED). This was a single-arm, phase IV, prospective clinical trial in sexually active men aged 45–75 years with BPH [International Prostate Symptom Score (IPSS) score ≥ 8] and ED [International Index of Erectile Function-Erectile Function (IIEF-EF) score ≤ 25] who were taking tamsulosin 0.4 mg PR and tadalafil 5 mg. Eligible patients received FDC of tamsulosin+tadalafil (0.4 + 5 mg) capsules for 12 weeks. The endpoints included treatment-emergent adverse events (TEAEs), total IPSS, IPSS storage and voiding sub-scores, maximum urinary flow rate (Qmax), post-void residual (PVR) volume, IIEF-EF (questions 1–5 and 15) score, and IPSS quality of life (QoL) index. A total of 172 were enrolled. Overall, 12 TEAEs were reported in 10 (5.81

Abstract Objectives To evaluate the correlation between weight loss and quality of life as assessed by SF-36 (36 item shoer form survey) questionnaire in patients treated with Semaglutide injection for weight management Materials and Methods This phase III, multicentre, randomized, open-label, active-controlled clinical study (CTRI/2025/04/085487) was conducted across 22 study sites in India after receiving regulatory and ethics committee approvals. Total 267 adult patients with BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with the presence of at least one co-morbidity of hypertension, dyslipidaemia and/or type 2 diabetes mellitus were included. Patients were randomized to either test arm to receive synthetic semaglutide injection or reference arm to receive Wegovy® every week subcutaneously for 24 weeks. The primary endpoint was change in body-weight from baseline to week 24. Secondary endpoints included change in BMI, waist circumference, SF-36, and glycaemic measures in diabetic and non-diabetic patients. Safety assessments included incidence of TEAEs and anti-drug/neutralizing antibody. This post-hoc analysis was conducted to evaluate the correlation between weight loss and improvement in quality of life as assessed by SF-36 physical function score. Results The Pearson’s correlation coefficient between change in weight loss and SF-36 physical functioning score was −0.155 with P value = .0467 in test arm. The Pearson’s correlation coefficient between change in weight loss and SF-36 physical functioning score was -0.046 with P value = .6831 in reference arm. There is negative correlation between weight loss and change in SF-36 physical functioning score in both test and reference arm indicating greater reduction in weight loss is associated with more increase in SF-36 score signifying improvement is SF-36 total score. The correlation between weight loss and improvement in SF-36 physical functioning score was statistically significant in test arm. The statistical significance observed in the Pearson correlation analysis in test arm supports the robustness of this association. Conclusions This post-hoc analysis demonstrated that there is improvement in quality of life as measured by SF-36 physical function score with reduction in weight, in patients treated with semaglutide injection for weight management.

Background:Type 2 diabetes mellitus (T2DM) is the most common non-communicable disease affecting over 89.8 million adults in India. Evidence suggests long-acting glucagon-like peptide-1 (GLP-1) receptor agonist improves glycaemic control in the patients with T2DM. This phase 3 trial compared a novel semaglutide injection developed by Zydus Lifesciences Ltd. with the reference biologic in Indian adults with T2DM inadequately controlled on metformin. Methods:In this multicentre, randomised study, 314 patients aged 18-65 years with HbA1c 7.0-10.5 % were randomised 1:1 to once-weekly semaglutide injection (test) or reference semaglutide for 24 weeks. Doses were titrated according to glycaemic targets. The primary endpoint was change in HbA1c at 24 weeks (pre-specified non-inferiority margin of 0.4 percentage points). Secondary endpoints included changes in fasting and post-prandial glucose, body weight, BMI, lipid profile, blood pressure, rescue medication use, safety profile and anti-drug antibody formation. Analyses were conducted on the modified intent-to-treat (mITT) population. Results:Of 314 randomised participants, 274 completed the trial (133 in the test arm and 141 in the comparator arm). HbA1c decreased from 8.36 % to 6.81 % in the test group and from 8.36 % to 6.79 % in the comparator, with a least-squares mean difference of -0.0038 % (95 % CI -0.20 to 0.19), meeting the pre-specified non-inferiority margin. Reductions in body weight (-4.59 vs -4.42 kg), BMI (-1.76 vs -1.68 kg/m2), fasting plasma glucose (-37.5 vs -39.0 mg/dL) and post-prandial plasma glucose (-54.5 vs -55.7 mg/dL) at week 24 were comparable between the groups. Treatment-emergent adverse events (TEAEs) were reported in 58.6 % of patients in the test group and 61.8 % of patients in the comparator group, respectively. Most events were mild and no serious adverse events occurred. Hypoglycaemia was infrequent and mild (1.9 % vs 0 %). Anti-drug antibodies were detected in 2.23 % of samples and had no impact on efficacy. Conclusions:This novel formulation of once-weekly semaglutide injection demonstrated non-inferior glycaemic efficacy, safety & immunogenicity to the reference product in Indian adults with type 2 diabetes. Trial registration:Clinical Trials Registry-India (CTRI/2025/03/082615).

INTRODUCTION:Heart failure with preserved ejection fraction (HFpEF) represents approximately 50% of all heart failure cases and lacks effective treatments. Chronotropic incompetence contributes to exercise intolerance in these patients. This study evaluated the safety and efficacy of blood pressure-adaptive atrial pacing (BPAP) vs standard bradycardia pacing (STD) in hypertensive patients with HFpEF. METHODS:In this prospective, double-blind, randomized, self-controlled crossover study, 16 patients (mean age: 62.7 ± 10.9 years; 6% female; left ventricular ejection fraction 55.3 ± 3.8%) with treated hypertension and implanted dual-chamber pacemakers underwent two 3-week treatment phases (BPAP and STD) in random order. The BPAP algorithm-modulated atrial pacing rate in response to home blood pressure readings. Endpoints included the Minnesota Living With Heart Failure (MLWHF) score, New York Heart Association (NYHA) class, 6-minute walk test (6MWT), and modified Bruce treadmill test. RESULTS:BPAP improved MLWHF score by an additional 15% from baseline (P = .0288), whereas STD showed a non-significant 3% worsening. Exercise time increased significantly during BPAP (+83.2 ± 55.6 s, P = .005) but not during STD (+70.8 ± 84.4 s, P = .095). The 6MWT distance rose by 35.8 ± 29.9 m during BPAP (P = .003) vs minimal change with STD (+8.2 ± 40.1 m, P = .6). NYHA class improved in 55.6% of BPAP patients vs 11% with STD (P = .0455). Mean heart rate was higher during BPAP (83.8 ± 8.3 bpm) than STD (72.9 ± 12.0 bpm, P < .0001), with no difference in systolic blood pressure (137.5 ± 14.9 vs 138.6 ± 14.0 mmHg, P = .68). No adverse events occurred. CONCLUSION:In hypertensive patients with HFpEF and implanted pacemakers, BPAP safely improved exercise capacity and functional status compared to standard pacing. The approach demonstrates feasibility of home-based blood pressure-modulated pacing for physiologic rate adaptation. (NCT06036186).