-
Stem Cells Translational Medicine Aug 2023The progressive appreciation that multiple types of RNAs regulate virtually all aspects of tissue function and the availability of effective tools to deliver RNAs in... (Review)
Review
The progressive appreciation that multiple types of RNAs regulate virtually all aspects of tissue function and the availability of effective tools to deliver RNAs in vivo now offers unprecedented possibilities for obtaining RNA-based therapeutics. For the heart, RNA therapies can be developed that stimulate endogenous repair after cardiac damage. Applications in this area include acute cardioprotection after ischemia or cancer chemotherapy, therapeutic angiogenesis to promote new blood vessel formation, regeneration to form new cardiac mass, and editing of mutations to cure inherited cardiac disease. While the potential of RNA therapeutics for all these conditions is exciting, the field is still in its infancy. A number of roadblocks need to be overcome for RNA therapies to become effective, in particular, related to the problem of delivering RNA medicines into the cells and targeting them specifically to the heart.
Topics: Heart; Regeneration; RNA, Antisense; Aptamers, Nucleotide; RNA Interference; RNA, Guide, CRISPR-Cas Systems; Gene Editing; Humans; Animals
PubMed: 37440203
DOI: 10.1093/stcltm/szad038 -
Trends in Pharmacological Sciences Oct 2020RNA-based medicine is receiving growing attention for its diverse roles and potential therapeutic capacity. The largest obstacle in its clinical translation remains... (Review)
Review
RNA-based medicine is receiving growing attention for its diverse roles and potential therapeutic capacity. The largest obstacle in its clinical translation remains identifying a safe and effective delivery system. Studies investigating RNA therapeutics in pulmonary diseases have rapidly expanded and drug administration by inhalation allows the direct delivery of RNA therapeutics to the target site of action while minimizing systemic exposure. In this review, we highlight recent developments in pulmonary RNA delivery systems with the use of nonviral vectors. We also discuss the major knowledge gaps that require thorough investigation and provide insights that will help advance this exciting field towards the bedside.
Topics: Administration, Inhalation; Humans; RNA; RNA Interference; RNA, Small Interfering
PubMed: 32893004
DOI: 10.1016/j.tips.2020.08.002 -
Journal of Controlled Release :... Sep 2020Rheumatoid arthritis (RA) is a common clinical inflammatory disease of the autoimmune system manifested by persistent synovitis, cartilage damage and even deformities.... (Review)
Review
Rheumatoid arthritis (RA) is a common clinical inflammatory disease of the autoimmune system manifested by persistent synovitis, cartilage damage and even deformities. Despite significant progress in the clinical treatment of RA, long-term administration of anti-rheumatic drugs can cause a series of problems, including infections, gastrointestinal reactions, and abnormal liver and kidney functions. The emergence of RNA interference (RNAi) drugs has brought new hope for the treatment of RA. Designing a reasonable vector for RNAi drugs will greatly expand the application prospects of RNAi. Nanoparticles as a promising drug carrier provide reliable support for RNAi drugs. The review summarizes the pathogenesis of RA as a possible target for small interference RNA (siRNA) design. At the same time, the review also analyzes the nanoparticles used in siRNA carriers in recent years, laying the foundation and prospect for the next step in the development of intelligent nanocarriers.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Nanoparticles; RNA Interference; RNA, Small Interfering
PubMed: 32653501
DOI: 10.1016/j.jconrel.2020.07.006 -
Molecular Cancer Mar 2023PIWI proteins have a strong correlation with PIWI-interacting RNAs (piRNAs), which are significant in development and reproduction of organisms. Recently, emerging... (Review)
Review
PIWI proteins have a strong correlation with PIWI-interacting RNAs (piRNAs), which are significant in development and reproduction of organisms. Recently, emerging evidences have indicated that apart from the reproductive function, PIWI/piRNAs with abnormal expression, also involve greatly in varieties of human cancers. Moreover, human PIWI proteins are usually expressed only in germ cells and hardly in somatic cells, so the abnormal expression of PIWI proteins in different types of cancer offer a promising opportunity for precision medicine. In this review, we discussed current researches about the biogenesis of piRNA, its epigenetic regulatory mechanisms in human cancers, such as N6-methyladenosine (mA) methylation, histone modifications, DNA methylation and RNA interference, providing novel insights into the markers for clinical diagnosis, treatment and prognosis in human cancers.
Topics: Humans; Piwi-Interacting RNA; Neoplasms; Epigenesis, Genetic; DNA Methylation; RNA Interference
PubMed: 36882835
DOI: 10.1186/s12943-023-01749-3 -
Nature Plants Sep 2023Small RNA (sRNA)-mediated trans-kingdom RNA interference (RNAi) between host and pathogen has been demonstrated and utilized. However, interspecies RNAi in rhizospheric...
Small RNA (sRNA)-mediated trans-kingdom RNA interference (RNAi) between host and pathogen has been demonstrated and utilized. However, interspecies RNAi in rhizospheric microorganisms remains elusive. In this study, we developed a microbe-induced gene silencing (MIGS) technology by using a rhizospheric beneficial fungus, Trichoderma harzianum, to exploit an RNAi engineering microbe and two soil-borne pathogenic fungi, Verticillium dahliae and Fusarium oxysporum, as RNAi recipients. We first detected the feasibility of MIGS in inducing GFP silencing in V. dahliae. Then by targeting a fungal essential gene, we further demonstrated the effectiveness of MIGS in inhibiting fungal growth and protecting dicotyledon cotton and monocotyledon rice plants against V. dahliae and F. oxysporum. We also showed steerable MIGS specificity based on a selected target sequence. Our data verify interspecies RNAi in rhizospheric fungi and the potential application of MIGS in crop protection. In addition, the in situ propagation of a rhizospheric beneficial microbe would be optimal in ensuring the stability and sustainability of sRNAs, avoiding the use of nanomaterials to carry chemically synthetic sRNAs. Our finding reveals that exploiting MIGS-based biofungicides would offer straightforward design and implementation, without the need of host genetic modification, in crop protection against phytopathogens.
Topics: Crop Protection; Gene Silencing; RNA Interference; Gene Editing; Genes, Fungal
PubMed: 37653339
DOI: 10.1038/s41477-023-01507-9 -
Plant & Cell Physiology May 2024Trans-species RNA interference (RNAi) occurs naturally when small RNAs (sRNAs) silence genes in species different from their origin. This phenomenon has been observed... (Review)
Review
Trans-species RNA interference (RNAi) occurs naturally when small RNAs (sRNAs) silence genes in species different from their origin. This phenomenon has been observed between plants and various organisms including fungi, animals and other plant species. Understanding the mechanisms used in natural cases of trans-species RNAi, such as sRNA processing and movement, will enable more effective development of crop protection methods using host-induced gene silencing (HIGS). Recent progress has been made in understanding the mechanisms of cell-to-cell and long-distance movement of sRNAs within individual plants. This increased understanding of endogenous plant sRNA movement may be translatable to trans-species sRNA movement. Here, we review diverse cases of natural trans-species RNAi focusing on current theories regarding intercellular and long-distance sRNA movement. We also touch on trans-species sRNA evolution, highlighting its research potential and its role in improving the efficacy of HIGS.
Topics: RNA Interference; Plants; RNA, Plant; RNA, Small Interfering; Animals
PubMed: 38288670
DOI: 10.1093/pcp/pcae012 -
The New Phytologist Oct 2023RNA interference (RNAi) is arguably one of the more versatile mechanisms in cell biology, facilitating the fine regulation of gene expression and protection against... (Review)
Review
RNA interference (RNAi) is arguably one of the more versatile mechanisms in cell biology, facilitating the fine regulation of gene expression and protection against mobile genomic elements, whilst also constituting a key aspect of induced plant immunity. More recently, the use of this mechanism to regulate gene expression in heterospecific partners - cross-kingdom RNAi (ckRNAi) - has been shown to form a critical part of bidirectional interactions between hosts and endosymbionts, regulating the interplay between microbial infection mechanisms and host immunity. Here, we review the current understanding of ckRNAi as it relates to interactions between plants and their pathogenic and mutualistic endosymbionts, with particular emphasis on evidence in support of ckRNAi in the arbuscular mycorrhizal symbiosis.
Topics: Symbiosis; Mycorrhizae; RNA Interference; Plants
PubMed: 37452489
DOI: 10.1111/nph.19122 -
Current Opinion in Plant Biology Jun 2021When an mRNA enters into the RNA degradation pathway called RNA interference (RNAi), it is cleaved into small interfering RNAs (siRNAs) that then target complementary... (Review)
Review
When an mRNA enters into the RNA degradation pathway called RNA interference (RNAi), it is cleaved into small interfering RNAs (siRNAs) that then target complementary mRNAs for destruction. The consequence of entry into RNAi is mRNA degradation, post-transcriptional silencing and in some cases transcriptional silencing. RNAi functions as a defense against transposable element and virus activity, and in plants, RNAi additionally plays a role in development by regulating some genes. However, it is unknown how specific transcripts are selected for RNAi, and how most genic mRNAs steer clear. This Current Opinion article explores the key question of how RNAs are selected for entry into RNAi, and proposes models that enable the cell to distinguish between transcripts to translate versus destroy.
Topics: DNA Transposable Elements; Plants; RNA Interference; RNA, Messenger; RNA, Small Interfering
PubMed: 33657510
DOI: 10.1016/j.pbi.2021.102014 -
Virus Genes Oct 2017After 30 years of retroviral vector research it became clear that the parental viruses can be both friend and foe. Especially human immunodeficiency virus sparked a... (Review)
Review
After 30 years of retroviral vector research it became clear that the parental viruses can be both friend and foe. Especially human immunodeficiency virus sparked a global pandemic, but could be converted into a versatile tool for cell therapy. For all retroviral genera, the way from virus to vector was similar resulting in split-vector systems based on the separation of the genes needed for vector particle formation and transgene expression. The first gene therapy trials, although clinically effective, revealed the genotoxicity of retroviral vectors caused by insertional mutagenesis. This issue was solved using self-inactivating vectors carrying weaker cellular promoters. Further fine-tuning was able to generate inducible systems. The current toolbox also contains vectors for the generation of induced pluripotent stem cells or efficient RNA interference. More recently the application of CRISPR-Cas9-mediated gene editing led to the development of genome-wide small guide RNA libraries targeting all human genes and single lentiviral vectors for an easy delivery of Cas9.
Topics: Animals; Genetic Therapy; Genetic Vectors; Humans; Lentivirus; Promoter Regions, Genetic; RNA Interference; Retroviridae; Transgenes
PubMed: 28762206
DOI: 10.1007/s11262-017-1489-0 -
Plant Science : An International... Jan 2019Non-cell autonomous RNA silencing can spread from cell to cell and over long-distances in animals and plants. This process is genetically determined and requires mobile... (Review)
Review
Non-cell autonomous RNA silencing can spread from cell to cell and over long-distances in animals and plants. This process is genetically determined and requires mobile RNA signals. Genetic requirement and molecular nature of the mobile signals for non-cell-autonomous RNA silencing were intensively investigated in past few decades. No consensus dogma for mobile silencing can be reached in plants, yet published data are sometimes inconsistent and controversial. Thus, the genetic requirements and molecular signals involved in plant mobile silencing are still poorly understood. This article revisits our present understanding of intercellular and systemic non-cell autonomous RNA silencing, and summarises current debates on RNA signals for mobile silencing. In particular, we discuss new evidence on siRNA mobility, a DCL2-dependent genetic network for mobile silencing and its potential biological relevance as well as 22 nt siRNA being a mobile signal for non-cell-autonomous silencing in both Arabidopsis and Nicotiana benthamiana. This sets up a new trend in unravelling genetic components and small RNA signal molecules for mobile silencing in (across) plants and other organisms of different kingdoms. Finally we raise several outstanding questions that need to be addressed in future plant silencing research.
Topics: Cell Communication; Models, Genetic; Plants; RNA Interference
PubMed: 30471724
DOI: 10.1016/j.plantsci.2018.10.025