Osteoarthritis (OA) is a chronic disorder caused by degenerative changes in articular cartilage, which are mainly manifests as degeneration of cartilage, subchondral bone remodeling, as well as synovial inflammation. Over the next few decades, OA and its burden will continue to increase worldwide, posing a major public health challenge for the foreseeable future. Treatment for OA includes non-pharmacological, pharmacological, and surgical treatments. Existing conservative treatments and joint surgery can only alleviate the symptoms and cannot be cured, so new therapies for OA are urgently needed. Since advances in the understanding of OA pathophysiology, researchers have identified some potential therapeutic targets against degeneration of cartilage, subchondral bone remodeling and synovial inflammation, enabling development of the disease-modifying OA drugs (DMOADs). Additionally, a number of new technologies are also being investigated for treating OA, such as RNA interference (RNAi), CRISPR/Cas9 and PROTAC. The goal of this review is to describe the current development status of DMOADs and to discuss the potential of emerging therapeutic approaches for treating OA, thus providing a reference for OA treatments.

While significant progress has been made in understanding and applying gene silencing mechanisms and the treatment of human diseases, there have been still several obstacles in therapeutic use. For the first time, ONPATTRO, as the first small interfering RNA (siRNA) based drug was invented in 2018 for treatment of hTTR with polyneuropathy. Additionally, four other siRNA based drugs naming Givosiran, Inclisiran, Lumasiran, and Vutrisiran have been approved by the US Food and Drug Administration and the European Medicines Agency for clinical use by hitherto. In this review, we have discussed the key and promising advances in the development of siRNA-based drugs in preclinical and clinical stages, the impact of these molecules in bacterial and viral infection diseases, delivery system issues, the impact of administration methods, limitations of siRNA application and how to overcome them and a glimpse into future developments.

Malaria is a major public health concern. The development of parasite-based vaccine RTS/AS01 has some therapeutic value but its lower efficacy is one of the major limitations. Mosquito-based transmission-blocking vaccines could have a higher potential for parasite inhibition within the mosquitoes. Several genes of mosquito midgut, salivary gland, hemolymph, etc. get activate in response to the Plasmodium-infected blood and helps in parasite invasion directly or indirectly inside the mosquito. The studies of such genes provided a new insight into developing the more efficient vaccines. In the field of malaria genetics research, RNAi has become an innovative strategy used to identify mosquito candidate genes for transmission-blocking vaccines. This review targeted the gene studies that have been conducted in the period 2000-2023 in different malaria vectors against different malarial parasites using the RNAi approach to reveal mosquito novel gene candidates for vaccine development.

The year 2023 marks the 25th anniversary of the discovery of RNAi. RNAi-based therapeutics enable sequence-specific gene knockdown by eliminating target RNA molecules through complementary base-pairing. A systematic review of published and ongoing clinical trials was performed. Web of Science, PubMed, and Embase were searched from January 1, 1998, to December 30, 2022 for clinical trials using RNAi. Following inclusion, data from the articles were extracted according to a predefined protocol. A total of 90 trials published in 81 articles were included. In addition, ongoing clinical trials were retrieved from ClinicalTrials.gov, resulting in the inclusion of 48 trials. We investigated how maturation of RNAi-based therapeutics and developments in delivery platforms, administration routes, and potential targets shape the current landscape of clinically applied RNAi. Notably, most contemporary clinical trials used either N-acetylgalactosamine delivery and subcutaneous administration or lipid nanoparticle delivery and intravenous administration. In conclusion, RNAi therapeutics have gained great momentum during the past decade, resulting in five approved therapeutics targeting the liver for treatment of severe diseases, and the trajectory depicted by the ongoing trials emphasizes that even more RNAi-based medicines also targeting extra-hepatic tissues are likely to be available in the years to come.

The Arachnida subclass of Acari comprises many harmful pests that threaten agriculture as well as animal health, including herbivorous spider mites, the bee parasite Varroa, the poultry mite Dermanyssus and several species of ticks. Especially in agriculture, acaricides are often used intensively to minimize the damage they inflict, promoting the development of resistance. Beneficial predatory mites used in biological control are also subjected to acaricide selection in the field. The development and use of new genetic and genomic tools such as genome and transcriptome sequencing, bulked segregant analysis (QTL mapping), and reverse genetics via RNAi or CRISPR/Cas9, have greatly increased our understanding of the molecular genetic mechanisms of resistance in Acari, especially in the spider mite Tetranychus urticae which emerged as a model species. These new techniques allowed to uncover and validate new resistance mutations in a larger range of species. In addition, they provided an impetus to start elucidating more challenging questions on mechanisms of gene regulation of detoxification associated with resistance.

The last few years have witnessed the emergence of alternative measures to control plant parasitic nematodes (PPNs). We briefly reviewed the potential of compost and the direct or indirect roles of soil-dwelling organisms against PPNs. We compiled and assessed the most intensively researched factors of suppressivity. Municipal green waste (MGW) was identified and profiled. We found that compost, with or without beneficial microorganisms as biocontrol agents (BCAs) against PPNs, were shown to have mechanisms for the control of plant parasitic nematodes. Compost supports a diverse microbiome, introduces and enhances populations of antagonistic microorganisms, releases nematicidal compounds, increases the tolerance and resistance of plants, and encourages the establishment of a \"soil environment\" that is unsuitable for PPNs. Our compilation of recent papers reveals that while the scope of research on compost and BCAs is extensive, the role of MGW-based compost (MGWC) in the control of PPNs has been given less attention. We conclude that the most environmentally friendly and long-term, sustainable form of PPN control is to encourage and enhance the soil microbiome. MGW is a valuable resource material produced in significant amounts worldwide. More studies are suggested on the use of MGWC, because it has a considerable potential to create and maintain soil suppressivity against PPNs. To expand knowledge, future research directions shall include trials investigating MGWC, inoculated with BCAs.

RNA interference (RNAi) shows great potential in the treatment of varying cancer and genetic disorders. The lack of safe and effective delivery methods is an ongoing challenge to realize the full potential of RNAi-based therapeutics. pH-responsive hybrid nanoparticle is a promising non-virus platform for small interfering RNA (siRNA) delivery with unique properties including the robust response to the acidic microenvironment and the capability of theranostic and combined therapeutics. The mechanism of RNAi and the delivery barriers for RNAi-based therapeutics are first discussed. Then, the general patterns of pH-response and the typical construction of hybrid nanoparticles are demonstrated. The recent advances in pH-responsive organic-inorganic hybrid nanoparticles for siRNA delivery are highlighted, in particular, how pH-response of ionizable groups, acid-labile bonds, and decomposition of inorganic components affect the physicochemical properties of hybrid nanoparticles and benefit the cellular uptake and intracellular trafficking of siRNA payloads are discussed. At last, the remaining problems and the prospects for pH-responsive hybrid nanoparticles for siRNA delivery are analyzed.

Amyotrophic lateral sclerosis (ALS) has historically posed unique challenges for gene-therapy-based approaches, due to a paucity of therapeutic targets as well as the difficulty of accessing both the brain and spinal cord. Recent advances in our understanding of disease mechanism and ALS genetics, however, have combined with tremendous strides in CNS targeting, gene delivery, and gene editing and knockdown techniques to open new horizons of therapeutic possibility. Gene therapy clinical trials are currently underway for ALS patients with SOD1 mutations, C9orf72 hexanucleotide repeat expansions, ATXN2 trinucleotide expansions, and FUS mutations, as well as sporadic disease without known genetic cause. In this review, we provide an in-depth exploration of the state of ALS-directed gene therapy, including antisense oligonucleotides, RNA interference, CRISPR, adeno-associated virus (AAV)-mediated trophic support, and antibody-based methods. We discuss how each of these approaches has been implemented across known genetic causes as well as sporadic ALS, reviewing preclinical studies as well as completed and ongoing human clinical trials. We highlight the transformative potential of these evolving technologies as the gene therapy field advances toward a true disease-modifying treatment for this devastating illness.

Colorado potato beetle, CPB (Leptinotarsa decemlineata Say), is one of the most important pests of the potato globally. Larvae and adults can cause complete defoliation of potato plant leaves and can lead to a large yield loss. The insect has been successfully suppressed by insecticides; however, over time, has developed resistance to insecticides from various chemical groups, and its once successful control has diminished. The number of available active chemical control substances is decreasing with the process of testing, and registering new products on the market are time-consuming and expensive, with the possibility of resistance ever present. All of these concerns have led to the search for new methods to control CPB and efficient tools to assist with the detection of resistant variants and monitoring of resistant populations. Current strategies that may aid in slowing resistance include gene silencing by RNA interference (RNAi). RNAi, besides providing an efficient tool for gene functional studies, represents a safe, efficient, and eco-friendly strategy for CPB control. Genetically modified (GM) crops that produce the toxins of Bacillus thuringiensis (Bt) have many advantages over agro-technical, mechanical, biological, and chemical measures. However, pest resistance that may occur and public acceptance of GM modified food crops are the main problems associated with Bt crops. Recent developments in the speed, cost, and accuracy of next generation sequencing are revolutionizing the discovery of single nucleotide polymorphisms (SNPs) and field of population genomics. There is a need for effective resistance monitoring programs that are capable of the early detection of resistance and successful implementation of integrated resistance management (IRM). The main focus of this review is on new technologies for CPB control (RNAi) and tools (SNPs) for detection of resistant CPB populations.

While much effort has been put into understanding vitellogenesis in insects and other organisms, much less is known of this process in ticks. There are several steps that facilitate yolk formation in developing oocytes of which the vitellogenin receptor (VgR) is a key component. The tick VgR binds vitellogenin (Vg) circulating in the hemolymph to initiate receptor-mediated endocytosis and its transformation into vitellin (Vn). The conversion of Vg into Vn, the final form of the yolk protein, occurs inside oocytes of the female tick ovary. Vn is critical to tick embryos since it serves as the nutritional source for their development, survival, and reproduction. Recent studies also suggest that pathogenic microbes, i.e., Babesia spp., that rely on ticks for propagation and dissemination likely \"hitchhike\" onto Vg molecules as they enter developing oocytes through the VgR. Suppressing VgR messenger RNA synthesis via RNA interference (RNAi) completely blocked Babesia spp. transmission into developing tick oocytes, thereby inhibiting vertical transmission of these pathogenic microbes from female to eggs. To date, VgRs from only four tick species, Dermacentor variabilis, Rhipicephalus microplus, Amblyomma hebraeum, and Haemaphysalis longicornis, have been fully sequenced and characterized. In contrast, many more VgRs have been described in various insect species. VgR is a critical component in egg formation and maturation that can serve as a precise target for tick control. However, additional research will help identify unique residues within the receptor that are specific to ticks or other arthropod disease vectors while avoiding cross-reactivity with non-target species. Detailed knowledge of the molecular structure and functional role of tick VgRs will enable development of novel vaccines to control ticks and tick-borne diseases.