scholarly journals RNA interference-based technology: what role in animal agriculture?

2017 ◽  
Vol 57 (1) ◽  
pp. 1 ◽  
Author(s):  
B. J. Bradford ◽  
C. A. Cooper ◽  
M. L. Tizard ◽  
T. J. Doran ◽  
T. M. Hinton
Keyword(s):  
Rna Interference ◽  
Genome Engineering ◽  
Sirna Delivery ◽  
Protein Product ◽  
Target Cells ◽  
Shrna Expression ◽  
Animal Agriculture ◽  
Transgenic Expression ◽  
Regulatory Processes ◽  
Adverse Environmental Conditions

Animal agriculture faces a broad array of challenges, ranging from disease threats to adverse environmental conditions, while attempting to increase productivity using fewer resources. RNA interference (RNAi) is a biological phenomenon with the potential to provide novel solutions to some of these challenges. Discovered just 20 years ago, the mechanisms underlying RNAi are now well described in plants and animals. Intracellular double-stranded RNA triggers a conserved response that leads to cleavage and degradation of complementary mRNA strands, thereby preventing production of the corresponding protein product. RNAi can be naturally induced by expression of endogenous microRNA, which are critical in the regulation of protein synthesis, providing a mechanism for rapid adaptation of physiological function. This endogenous pathway can be co-opted for targeted RNAi either through delivery of exogenous small interfering RNA (siRNA) into target cells or by transgenic expression of short hairpin RNA (shRNA). Potentially valuable RNAi targets for livestock include endogenous genes such as developmental regulators, transcripts involved in adaptations to new physiological states, immune response mediators, and also exogenous genes such as those encoded by viruses. RNAi approaches have shown promise in cell culture and rodent models as well as some livestock studies, but technical and market barriers still need to be addressed before commercial applications of RNAi in animal agriculture can be realised. Key challenges for exogenous delivery of siRNA include appropriate formulation for physical delivery, internal transport and eventual cellular uptake of the siRNA; additionally, rigorous safety and residue studies in target species will be necessary for siRNA delivery nanoparticles currently under evaluation. However, genomic incorporation of shRNA can overcome these issues, but optimal promoters to drive shRNA expression are needed, and genetic engineering may attract more resistance from consumers than the use of exogenous siRNA. Despite these hurdles, the convergence of greater understanding of RNAi mechanisms, detailed descriptions of regulatory processes in animal development and disease, and breakthroughs in synthetic chemistry and genome engineering has created exciting possibilities for using RNAi to enhance the sustainability of animal agriculture.

scholarly journals Non-Viral Delivery and Therapeutic Application of Small Interfering RNAs

Acta Naturae ◽  
2013 ◽  
Vol 5 (3) ◽  
pp. 35-53 ◽  
Author(s):  
N. A. Nikitenko ◽  
V. S. Prassolov
Keyword(s):  
Rna Interference ◽  
Gene Expression Regulation ◽  
Sirna Delivery ◽  
Target Cells ◽  
Powerful Method ◽  
Small Interfering Rnas ◽  
Therapeutic Application ◽  
Rnai Technology ◽  
In Vivo Degradation

RNA interference (RNAi) is a powerful method used for gene expression regulation. The increasing knowledge about the molecular mechanism of this phenomenon creates new avenues for the application of the RNAi technology in the treatment of various human diseases. However, delivery of RNA interference mediators, small interfering RNAs (siRNAs), to target cells is a major hurdle. Effective and safe pharmacological use of siRNAs requires carriers that can deliver siRNA to its target site and the development of methods for protection of these fragile molecules from in vivo degradation. This review summarizes various strategies for siRNA delivery, including chemical modification and non-viral approaches, such as the polymer-based, peptide-based, lipid-based techniques, and inorganic nanosystems. The advantages, disadvantages, and prospects for the therapeutic application of these methods are also examined in this paper.

scholarly journals Delivery Systems for the Direct Application of siRNAs to Induce RNA Interference (RNAi) In Vivo

2006 ◽  
Vol 2006 ◽  
pp. 1-15 ◽  
Author(s):  
Achim Aigner
Keyword(s):  
Rna Interference ◽  
Sirna Delivery ◽  
Critical Factor ◽  
Delivery Systems ◽  
Tumor Xenograft ◽  
Target Cells ◽  
Specific Gene ◽  
Mouse Tumor ◽  
Small Interfering Rnas

RNA interference (RNAi) is a powerful method for specific gene silencing which may also lead to promising novel therapeutic strategies. It is mediated through small interfering RNAs (siRNAs) which sequence-specifically trigger the cleavage and subsequent degradation of their target mRNA. One critical factor is the ability to deliver intact siRNAs into target cells/organs in vivo. This review highlights the mechanism of RNAi and the guidelines for the design of optimal siRNAs. It gives an overview of studies based on the systemic or local application of naked siRNAs or the use of various nonviral siRNA delivery systems. One promising avenue is the the complexation of siRNAs with the polyethylenimine (PEI), which efficiently stabilizes siRNAs and, upon systemic administration, leads to the delivery of the intact siRNAs into different organs. The antitumorigenic effects of PEI/siRNA-mediated in vivo gene-targeting of tumor-relevant proteins like in mouse tumor xenograft models are described.

Nanostructured Hyaluronic Acid-based Materials for the Delivery of siRNA

2018 ◽  
Vol 24 (23) ◽  
pp. 2678-2691 ◽  
Author(s):  
Keval Shah ◽  
Sunita Chawla ◽  
Anuradha Gadeval ◽  
Goutham Reddy ◽  
Rahul Maheshwari ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Rna Interference ◽  
Sirna Delivery ◽  
Treatment Strategies ◽  
Aqueous Solubility ◽  
Micro Rna ◽  
Target Space ◽  
Significant Progress ◽  
Gene Therapies ◽  
Future Potential

Background: The search for the effective treatment strategies to combat a disease that is characterized by abnormal cell growth and known as cancer is still required to reach its destiny. To address the problem, recently several gene therapies based on novel RNA interference (RNAi) have been proposed such as siRNA, micro RNA, shRNA, etc. out of which, siRNAs (silencing RNA) promises to show significant progress in pharmacotherapy, including considerable expansion of the druggable target space and the possibility of treating cancer. Methods: This review aims to uncover the hyaluronic acid (HA) and HA-hybridized nanoplatforms for siRNA delivery systems with a particular focus on the discussion of available reports while addressing the future potential of HA-based treatment strategies. Results: HA modified siRNA delivery, as promised, provided better targeting potential in many types of cancers. In addition, it was able to modify the release of siRNA as well. Toxicity of HA is well mentioned however, the loophole is yet to be filled by exploring various remedies for overcoming toxicity. Conclusion: To overcome the problems associated with these emerging genetic tools, investigators have employed glycosaminoglycan HA-based biopolymers. This biopolymer offers a variety of properties such as biodegradability, biocompatibility, aqueous solubility, viscoelasticity, and non-immunogenicity.

DNA-binding and transcriptional properties of human transcription factor TFIID after mild proteolysis

1990 ◽  
Vol 10 (7) ◽  
pp. 3415-3420
Author(s):  
M W Van Dyke ◽  
M Sawadogo
Keyword(s):  
Transcription Factor ◽  
Transcription Initiation ◽  
Small Region ◽  
Protein Product ◽  
Differential Sensitivity ◽  
Yeast Cells ◽  
Promoter Regions ◽  
Regulatory Processes ◽  
Promoter Recognition ◽  
Transcription Complexes

The existence of separable functions within the human class II general transcription factor TFIID was probed for differential sensitivity to mild proteolytic treatment. Independent of whether TFIID was bound to DNA or free in solution, partial digestion with either one of a variety of nonspecific endoproteases generated a protease-resistant protein product that retained specific DNA recognition, as revealed by DNase I footprinting. However, in contrast to native TFIID, which interacts with the adenovirus major late (ML) promoter over a very broad DNA region, partially proteolyzed TFIID interacted with only a small region of the ML promoter immediately surrounding the TATA sequence. This novel footprint was very similar to that observed with the TATA factor purified from yeast cells. Partially proteolyzed human TFIID could form stable complexes that were resistant to challenge by exogenous templates. It could also nucleate the assembly of transcription complexes on the ML promoter with an efficiency comparable to that of native TFIID, yielding similar levels of transcription initiation. These results suggest a model in which the human TFIID protein is composed of at least two different regions or polypeptides: a protease-resistant "core," which by itself is sufficient for promoter recognition and basal transcriptional levels, and a protease-sensitive "tail," which interacts with downstream promoter regions and may be involved in regulatory processes.

scholarly journals Development of siRNA-Loaded Lipid Nanoparticles Targeting Long Non-Coding RNA LINC01257 as a Novel and Safe Therapeutic Approach for t(8;21) Pediatric Acute Myeloid Leukemia

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1681
Author(s):  
Patrick Connerty ◽  
Ernest Moles ◽  
Charles E. de Bock ◽  
Nisitha Jayatilleke ◽  
Jenny L. Smith ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Mononuclear Cells ◽  
Sirna Delivery ◽  
Standard Of Care ◽  
Lipid Nanoparticles ◽  
Protein Product ◽  
Peripheral Blood Mononuclear ◽  
Acute Myeloid

Standard of care therapies for children with acute myeloid leukemia (AML) cause potent off-target toxicity to healthy cells, highlighting the need to develop new therapeutic approaches that are safe and specific for leukemia cells. Long non-coding RNAs (lncRNAs) are an emerging and highly attractive therapeutic target in the treatment of cancer due to their oncogenic functions and selective expression in cancer cells. However, lncRNAs have historically been considered ‘undruggable’ targets because they do not encode for a protein product. Here, we describe the development of a new siRNA-loaded lipid nanoparticle for the therapeutic silencing of the novel oncogenic lncRNA LINC01257. Transcriptomic analysis of children with AML identified LINC01257 as specifically expressed in t(8;21) AML and absent in healthy patients. Using NxGen microfluidic technology, we efficiently and reproducibly packaged anti-LINC01257 siRNA (LNP-si-LINC01257) into lipid nanoparticles based on the FDA-approved Patisiran (Onpattro®) formulation. LNP-si-LINC01257 size and ζ-potential were determined by dynamic light scattering using a Malvern Zetasizer Ultra. LNP-si-LINC01257 internalization and siRNA delivery were verified by fluorescence microscopy and flow cytometry analysis. lncRNA knockdown was determined by RT-qPCR and cell viability was characterized by flow cytometry-based apoptosis assay. LNP-siRNA production yielded a mean LNP size of ~65 nm with PDI ≤0.22 along with a >85% siRNA encapsulation rate. LNP-siRNAs were efficiently taken up by Kasumi-1 cells (>95% of cells) and LNP-si-LINC01257 treatment was able to successfully ablate LINC01257 expression which was accompanied by a significant 55% reduction in total cell count following 48 h of treatment. In contrast, healthy peripheral blood mononuclear cells (PBMCs), which do not express LINC01257, were unaffected by LNP-si-LINC01257 treatment despite comparable levels of LNP-siRNA uptake. This is the first report demonstrating the use of LNP-assisted RNA interference modalities for the silencing of cancer-driving lncRNAs as a therapeutically viable and non-toxic approach in the management of AML.

scholarly journals Novel Fluorinated Spermine and Small Molecule PEI to Deliver Anti-PD-L1 and Anti-VEGF siRNA for Highly Efficient Tumor Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2058
Author(s):  
Yihui Zhang ◽  
Zihan Yuan ◽  
Yi Jin ◽  
Wenkai Zhang ◽  
Wei-En Yuan
Keyword(s):  
Gene Therapy ◽  
T Cells ◽  
Small Molecule ◽  
Tumor Therapy ◽  
Sirna Delivery ◽  
Death Receptor ◽  
Target Cells ◽  
Anti Vegf ◽  
Tumor Killing ◽  
Death Receptor Ligand

Small interfering RNA (siRNA) can specifically silence disease gene expression. This project investigated the overexpression of programmed death receptor ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF) on the surface of tumor cells. However, the main obstacle to the development of gene therapy drugs is the lack of an efficient delivery vector, which should be able to overcome multiple delivery barriers and protect siRNA to enter the target cells. Therefore, a novel fluorine-modified endogenous molecular carrier TFSPEI was constructed by linking fluorinated groups with hydrophobic and hydrophilic characteristics on the surface of PEI and spermine. The results showed that lower toxicity, higher endocytosis, and silencing efficiency were achieved. We found that the inhibition of VEGF targets can indirectly activate the immune response to promote the tumor-killing and invasion effects of T cells. The combined delivery of anti-VEGF siRNA and anti-PD-L1 siRNA could inhibit the expression of corresponding proteins, restore the anti-tumor function of T cells and inhibit the growth of neovascularization, and obtained significant anti-tumor effects. Therefore, this safe and efficient fluorinated spermine and small molecule PEI-based anti-PD-L1 and anti-VEGF siRNA delivery system is expected to provide a new strategy for gene therapy of tumors.

scholarly journals Structurally modulated codelivery of siRNA and Argonaute 2 for enhanced RNA interference

2018 ◽  
Vol 115 (12) ◽  
pp. E2696-E2705 ◽  
Author(s):  
Jiahe Li ◽  
Connie Wu ◽  
Wade Wang ◽  
Yanpu He ◽  
Elad Elkayam ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Rna Interference ◽  
Small Interfering Rna ◽  
Sirna Delivery ◽  
Effector Protein ◽  
Side Group ◽  
Argonaute 2 ◽  
Fundamental Research ◽  
Delivery Vehicles ◽  
Interfering Rna

Small interfering RNA (siRNA) represents a promising class of inhibitors in both fundamental research and the clinic. Numerous delivery vehicles have been developed to facilitate siRNA delivery. Nevertheless, achieving highly potent RNA interference (RNAi) toward clinical translation requires efficient formation of RNA-induced gene-silencing complex (RISC) in the cytoplasm. Here we coencapsulate siRNA and the central RNAi effector protein Argonaute 2 (Ago2) via different delivery carriers as a platform to augment RNAi. The physical clustering between siRNA and Ago2 is found to be indispensable for enhanced RNAi. Moreover, by utilizing polyamines bearing the same backbone but distinct cationic side-group arrangements of ethylene diamine repeats as the delivery vehicles, we find that the molecular structure of these polyamines modulates the degree of siRNA/Ago2-mediated improvement of RNAi. We apply this strategy to silence the oncogene STAT3 and significantly prolong survival in mice challenged with melanoma. Our findings suggest a paradigm for RNAi via the synergistic coassembly of RNA with helper proteins.

An Overview of nano delivery systems for targeting RNA interference-based therapy in ulcerative colitis

2021 ◽  
Vol 27 ◽  
Author(s):  
Iman Alfagih ◽  
Basmah Aldosari ◽  
Bushra AlQuadeib ◽  
Alanood Almurshedi ◽  
Murtaza Tambuwala
Keyword(s):  
Ulcerative Colitis ◽  
Rna Interference ◽  
Protein Expression ◽  
Messenger Rna ◽  
Delivery Systems ◽  
Target Cells ◽  
Intracellular Space ◽  
Therapeutic Benefits ◽  
Negative Effect

: Ulcerative colitis (UC) is one of the main subtypes of inflammatory bowel disease. UC has a negative effect on patients’ quality of life, and it is an important risk factor for the development of colitis-associated cancer. Patients with UC need to take medications for their entire life because no permanent cure is available. Therefore, approaches that target messenger RNA (mRNA) of proinflammatory cytokines or anti-inflammatory cytokines are needed to improve the safety of UC therapy and promote intestinal mucosa recovery. The major challenge facing RNA interference-based therapy is the delivery of RNA molecules to the intracellular space of target cells. Moreover, nonspecific and systemic protein expression inhibition can result in adverse effects and less therapeutic benefits. Thus, it is important to develop an efficient delivery strategy targeting the cytoplasm of target cells to avoid side effects caused by off-target protein expression inhibition. This review focuses on the most recent advances in the targeted nano delivery systems of siRNAs and mRNA that have shown in vivo efficacy.

Databases and bioinformatics tools for genome engineering in plants using RNA interference

2021 ◽  
pp. 773-786
Author(s):  
Rimsha Farooq ◽  
Khadim Hussain ◽  
Aftab Bashir ◽  
Kamran Rashid ◽  
Muhammad Ashraf
Keyword(s):  
Rna Interference ◽  
Genome Engineering ◽  
Bioinformatics Tools

Insect omics research coming of age1This review is part of a virtual symposium on recent advances in understanding a variety of complex regulatory processes in insect physiology and endocrinology, including development, metabolism, cold hardiness, food intake and digestion, and diuresis, through the use of omics technologies in the postgenomic era.

2012 ◽  
Vol 90 (4) ◽  
pp. 440-455 ◽  
Author(s):  
Bart Boerjan ◽  
Dries Cardoen ◽  
Rik Verdonck ◽  
Jelle Caers ◽  
Liliane Schoofs
Keyword(s):  
Rna Interference ◽  
Cold Hardiness ◽  
Model Organisms ◽  
Sequence Information ◽  
Huge Amount ◽  
Omics Technologies ◽  
Regulatory Processes ◽  
Biological Aspects ◽  
Insect Biology ◽  
Functional Inactivation

As more and more insect genomes are fully sequenced and annotated, omics technologies, including transcriptomic, proteomic, peptidomics, and metobolomic profiling, as well as bioinformatics, can be used to exploit this huge amount of sequence information for the study of different biological aspects of insect model organisms. Omics experiments are an elegant way to deliver candidate genes, the function of which can be further explored by genetic tools for functional inactivation or overexpression of the genes of interest. Such tools include mainly RNA interference and are currently being developed in diverse insect species. In this manuscript, we have reviewed how omics technologies were integrated and applied in insect biology.

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