Cancer is associated with single or multiple gene defects. Recently, much research has focused on incorporating genetic materials as one of the means to treat various types of carcinomas. RNA interference (RNAi) conveys an alternative genetic approach for cancer patients, especially when conventional medications fail. RNAi involves the inhibition of expression of specific messenger RNA that signals for uncontrollable cell growth and proliferation, most notably with carcinoma cells. This molecular technology is promising as genetic materials allow us to overcome issues associated with chemotherapeutic agents including organ damage associated with severe drug toxicities. Nonetheless, vast challenges impede successful gene therapy application, including low tumor localization, low stability and rapid clearance from the blood circulation. Owing to the limited treatment opportunities for the management of cancer, the development of effective siRNA carrier systems involving nanotherapeutics has been extensively explored. Over the past years, several siRNA nanotherapeutics have undergone a period of clinical investigation, with some demonstrating promising antitumor activities and safety profiles. Extensive observation of siRNA-nanoparticles is necessary to ensure commercial success. Therefore, this review mainly focuses on the progress of siRNAs-loaded nanoparticles that have undergone clinical trials for cancer treatment. The status of the siRNA nanotherapeutics is discussed, allowing comprehensive understanding of their gene-mediated therapeutics.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) outbreaks that resulted in a catastrophic threat to global health, with more than 500 million cases detected and 5.5 million deaths worldwide. Patients with a COVID-19 infection presented with clinical manifestations ranging from asymptomatic to severe symptoms, resulting in acute lung injury, acute respiratory distress syndrome, and even death. Immune dysregulation through delayed innate immune response or impairment of the adaptive immune response is the key contributor to the pathophysiology of COVID-19 and SARS-CoV-2-induced cytokine storm. Symptomatic and supportive therapy is the fundamental strategy in treating COVID-19 infection, including antivirals, steroid-based therapies, and cell-based immunotherapies. Various studies reported substantial effects of immune-based therapies for patients with COVID-19 to modulate the over-activated immune system while simultaneously refining the body’s ability to destroy the virus. However, challenges may arise from the complexity of the disease through the genetic variance of the virus itself and patient heterogeneity, causing increased transmissibility and heightened immune system evasion that rapidly change the intervention and prevention measures for SARS-CoV-2. Cell-based therapy, utilizing stem cells, dendritic cells, natural killer cells, and T cells, among others, are being extensively explored as other potential immunological approaches for preventing and treating SARS-CoV-2-affected patients the similar process was effectively proven in SARS-CoV-1 and MERS-CoV infections. This review provides detailed insights into the innate and adaptive immune response-mediated cell-based immunotherapies in COVID-19 patients. The immune response linking towards engineered autologous or allogenic immune cells for either treatment or preventive therapies is subsequently highlighted in an individual study or in combination with several existing treatments. Up-to-date data on completed and ongoing clinical trials of cell-based agents for preventing or treating COVID-19 are also outlined to provide a guide that can help in treatment decisions and future trials.

The emergence of seekRNA- and bridgeRNA-guided recombination has introduced a distinct paradigm in genome engineering by coupling programmable RNA-directed DNA recognition with recombinase-mediated insertion, excision, inversion, and genomic rearrangement without canonical double-strand breaks. Since their discovery in 2024, these systems have progressed rapidly from bacterial mobile genetic elements and mechanistic characterization to structural elucidation and programmable genome engineering in human cells. However, these advances remain distributed across foundational and rapidly emerging studies, creating a need for an integrated molecular perspective on their mechanisms, technological development, and position within contemporary genome engineering. This review synthesizes the molecular architecture, RNA-guided recognition, strand-exchange mechanisms, programmability, and engineering of seekRNA and bridgeRNA systems, with particular emphasis on complementary human-cell advances involving ISCro4 and engineered IS621. Whereas ISCro4 systems have enabled multikilobase DNA insertion, genomic excision, and near-megabase inversion, the enIS621–tebRNA platform has enabled scarless kilobase-scale integration across multiple human cell types, including proof-of-concept functional CD19 chimeric antigen receptor and factor IX gene insertion. The review further integrates recent genome-scale bacterial rewriting and Targetable Recombinase Assisted DNA Exchange (TRADE)-mediated DNA replacement, while benchmarking RNA-guided recombination against conventional site-specific recombination, clustered regularly interspaced short palindromic repeats (CRISPR)-based editing, Programmable Addition via Site-specific Targeting Elements (PASTE), CRISPR-associated transposases, and emerging large-payload genome-writing strategies, including kilobase-scale nickase-targeting (KNIT) editing, Prime Assembly, engineered R2 retrotransposons, and TransCRISTI. This comparative framework highlights a broader transition from programmable sequence modification toward direct engineering of genomic architecture, while identifying recognition-site constraints, mismatch-tolerant recombination, unintended recombination products, delivery, and genome-wide specificity as key translational barriers. By integrating foundational mechanisms with recent mammalian engineering, genome-scale bacterial rewriting, large-payload technologies, and emerging computational design strategies, this review provides a contemporary framework for defining the distinctive capabilities, current limitations, and future development of programmable RNA-guided DNA recombination.

I read with interest the manuscript entitled “Targeting Cancer Cell Signaling Using Precision Oncology Towards a Holistic Approach to Cancer Therapeutics”. Using a precision approach for targeting molecular signaling pathways is one of the hot topics...