Displaying publications 1 - 20 of 52 in total

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  1. Tekade RK
    Curr Pharm Des, 2015;21(31):4527-8.
    PMID: 26362643
    Matched MeSH terms: RNA Interference*
  2. Darsan Singh JK, Mat Jalaluddin NS, Sanan-Mishra N, Harikrishna JA
    Plant Cell Rep, 2019 Dec;38(12):1449-1463.
    PMID: 31350570 DOI: 10.1007/s00299-019-02446-6
    Recent developments in modern biotechnology such as the use of RNA interference (RNAi) have broadened the scope of crop genetic modification. RNAi strategies have led to significant achievements in crop protection against biotic and abiotic stresses, modification of plant traits, and yield improvement. As RNAi-derived varieties of crops become more useful in the field, it is important to examine the capacity of current regulatory systems to deal with such varieties, and to determine if changes are needed to improve the existing frameworks. We review the biosafety frameworks from the perspective of developing countries that are increasingly involved in modern biotechnology research, including RNAi applications, and make some recommendations. Malaysia and India have approved laws regulating living modified organisms and products thereof, highlighting that the use of any genetically modified step requires regulatory scrutiny. In view of production methods for exogenously applied double-stranded RNAs and potential risks from the resulting double-stranded RNA-based products, we argue that a process-based system may be inappropriate for the non-transformative RNAi technology. We here propose that the current legislation needs rewording to take account of the non-transgenic RNAi technology, and discuss the best alternative for regulatory systems in India and Malaysia in comparison with the existing frameworks in other countries.
    Matched MeSH terms: RNA Interference/physiology
  3. Nor Muhammad NA, Ramlee IA, Mohd Nor D, Satyavenathan MV, Rahmat NL, Awang A, et al.
    Data Brief, 2021 Feb;34:106638.
    PMID: 33365368 DOI: 10.1016/j.dib.2020.106638
    Cocoa bean (Theobroma cacao L.) is part of the global cocoa and chocolate industry valued at 44 billion US dollars in 2019. Cocoa pod borer (CPB), Conopomorpha cramerella is a major pest of cocoa in Malaysia and Indonesia that is responsible for the decline for cocoa production. They have been detected since 1980s. Unfortunately, current control strategies are inefficient for CPB management. Although biotechnological alternatives, including RNA interference (RNAi), have been proposed in recent years to control insect pests, characterizing the genetics of the target pest is essential for successful application of these emerging technologies. We generated a comprehensive RNA-seq dataset (135,915,430 clean reads) for larva and adult stages of CPB by using the Illumina HiseqTM 4000 system to increase the understanding of CPB in relation to molecular features. The CPB transcriptome was assembled de novo and annotated. The final assembled produced 249,280 unigenes, of which 75,929 unigenes annotated against NCBI NR database and were distributed among 156 KEGG pathways. The raw data were uploaded to SRA database and the BioProject ID is PRJNA553611. The transcriptomic dataset we present are the first reports of transcriptome information in CPB that is valuable for further exploration and understanding of CPB molecular pathways.
    Matched MeSH terms: RNA Interference
  4. Raja MAG, Katas H, Amjad MW
    Asian J Pharm Sci, 2019 Sep;14(5):497-510.
    PMID: 32104477 DOI: 10.1016/j.ajps.2018.12.005
    Upon the discovery of RNA interference (RNAi), canonical small interfering RNA (siRNA) has been recognized to trigger sequence-specific gene silencing. Despite the benefits of siRNAs as potential new drugs, there are obstacles still to be overcome, including off-target effects and immune stimulation. More recently, Dicer substrate siRNA (DsiRNA) has been introduced as an alternative to siRNA. Similarly, it also is proving to be potent and target-specific, while rendering less immune stimulation. DsiRNA is 25-30 nucleotides in length, and is further cleaved and processed by the Dicer enzyme. As with siRNA, it is crucial to design and develop a stable, safe, and efficient system for the delivery of DsiRNA into the cytoplasm of targeted cells. Several polymeric nanoparticle systems have been well established to load DsiRNA for in vitro and in vivo delivery, thereby overcoming a major hurdle in the therapeutic uses of DsiRNA. The present review focuses on a comparison of siRNA and DsiRNA on the basis of their design, mechanism, in vitro and in vivo delivery, and therapeutics.
    Matched MeSH terms: RNA Interference
  5. Kuche K, Maheshwari R, Tambe V, Mak KK, Jogi H, Raval N, et al.
    Nanoscale, 2018 May 17;10(19):8911-8937.
    PMID: 29722421 DOI: 10.1039/c8nr01383g
    The search for effective and non-invasive delivery modules to transport therapeutic molecules across skin has led to the discovery of a number of nanocarriers (viz.: liposomes, ethosomes, dendrimers, etc.) in the last few decades. However, available literature suggests that these delivery modules face several issues including poor stability, low encapsulation efficiency, and scale-up hurdles. Recently, carbon nanotubes (CNTs) emerged as a versatile tool to deliver therapeutics across skin. Superior stability, high loading capacity, well-developed synthesis protocol as well as ease of scale-up are some of the reason for growing interest in CNTs. CNTs have a unique physical architecture and a large surface area with unique surface chemistry that can be tailored for vivid biomedical applications. CNTs have been thus largely engaged in the development of transdermal systems such as tuneable hydrogels, programmable nonporous membranes, electroresponsive skin modalities, protein channel mimetic platforms, reverse iontophoresis, microneedles, and dermal buckypapers. In addition, CNTs were also employed in the development of RNA interference (RNAi) based therapeutics for correcting defective dermal genes. This review expounds the state-of-art synthesis methodologies, skin penetration mechanism, drug liberation profile, loading potential, characterization techniques, and transdermal applications along with a summary on patent/regulatory status and future scope of CNT based skin therapeutics.
    Matched MeSH terms: RNA Interference
  6. Intan Elya Suka, Nur Farhana Roslan, Zamri Zainal, Nurulhikma Md Isa, Bee LC
    Sains Malaysiana, 2018;47:1465-1471.
    Gen Proteolisis 6 (PRT6) merupakan gen yang memainkan peranan penting dalam tapak jalan N-end rule dan berfungsi
    sebagai enzim E3 ligase. PRT6 berperanan dalam pengenalan protein sasaran bagi proses degradasi. Objektif utama kajian
    ini adalah untuk mentransformasi konstruk RNAi PRT6 ke dalam tomato berperantarakan Agrobacterium tumefaciens.
    Ini bertujuan untuk memahami peranan tapak jalan N-end rule semasa proses pemasakan buah. Beberapa faktor yang
    memberi kesan kepada transformasi seperti masa ko-penanaman dan juga kepekatan antibiotik yang digunakan telah
    dioptimumkan. Keputusan kajian menunjukkan pengeraman kotiledon selama 48 jam pada medium ko-penanaman dapat
    meningkatkan penghasilan kalus sebanyak 61% manakala penggunaan 500 mg/L antibiotik karbenisilin dalam medium
    regenerasi pucuk dapat mengurangkan kontaminasi A. tumefaciens sehingga 5.2%. Selain itu, strain A. tumefaciens
    C58 merupakan strain A. tumefaciens yang paling sesuai digunakan sebagai perantara dalam kajian ini. Tindak balas
    berantai polimerase (PCR) telah dijalankan pada pucuk yang terhasil untuk mengesahkan integrasi fragmen PRT6 ke dalam
    genom tomato. Berdasarkan analisis PCR, kesemua tujuh pucuk putatif transgenik adalah merupakan transforman positif.
    Matched MeSH terms: RNA Interference
  7. Sekeli R, Abdullah JO, Namasivayam P, Muda P, Abu Bakar UK, Yeong WC, et al.
    Molecules, 2014 Jun 19;19(6):8350-62.
    PMID: 24950439 DOI: 10.3390/molecules19068350
    The purpose of this study was to evaluate the effectiveness of using RNA interference in down regulating the expression of 1-aminocyclopropane-1-carboxylic acid oxidase gene in Eksotika papaya. One-month old embryogenic calli were separately transformed with Agrobacterium strain LBA 4404 harbouring the three different RNAi pOpOff2 constructs bearing the 1-aminocyclopropane-1-carboxylic acid oxidase gene. A total of 176 putative transformed lines were produced from 15,000 calli transformed, selected, then regenerated on medium supplemented with kanamycin. Integration and expression of the targeted gene in putatively transformed lines were verified by PCR and real-time RT-PCR. Confined field evaluation of a total of 31 putative transgenic lines planted showed a knockdown expression of the targeted ACO1 and ACO2 genes in 13 lines, which required more than 8 days to achieve the full yellow colour (Index 6). Fruits harvested from lines pRNAiACO2 L2-9 and pRNAiACO1 L2 exhibited about 20 and 14 days extended post-harvest shelf life to reach Index 6, respectively. The total soluble solids contents of the fruits ranged from 11 to 14° Brix, a range similar to fruits from non-transformed, wild type seed-derived plants.
    Matched MeSH terms: RNA Interference/physiology
  8. Alhoot MA, Wang SM, Sekaran SD
    PLoS One, 2012;7(3):e34060.
    PMID: 22457813 DOI: 10.1371/journal.pone.0034060
    Dengue virus-host cell interaction initiates when the virus binds to the attachment receptors followed by endocytic internalization of the virus particle. Successful entry into the cell is necessary for infection initiation. Currently, there is no protective vaccine or antiviral treatment for dengue infection. Targeting the viral entry pathway has become an attractive therapeutic strategy to block infection. This study aimed to investigate the effect of silencing the GRP78 and clathrin-mediated endocytosis on dengue virus entry and multiplication into HepG2 cells.
    Matched MeSH terms: RNA Interference*
  9. Ponthan F, Yusoff NM, Soria NM, Heidenreich O, Coffey K
    Curr Protoc Mol Biol, 2015 Jul 01;111:26.2.1-26.2.17.
    PMID: 26131850 DOI: 10.1002/0471142727.mb2602s111
    This unit provides information how to use short interfering RNA (siRNA) for sequence-specific gene silencing in mammalian cells. Several methods for siRNA generation and optimization, as well as recommendations for cell transfection and transduction, are presented.
    Matched MeSH terms: RNA Interference*
  10. Mohd Zain MZ, Ismail NH, Ahmad N, Sulong S, Karsani SA, Abdul Majid N
    Mol Biol Rep, 2020 Oct;47(10):7735-7743.
    PMID: 32959195 DOI: 10.1007/s11033-020-05848-y
    Telomerase is a cancer promoting ribonucleoprotein complex and is a potential therapeutic target for cancer. In this study, the effects of telomerase downregulation on the whole cell proteome were investigated. Understanding how the effect of downregulation on the whole proteome profile will generate a greater understanding of the possible roles played by telomerase in cancer. Downregulation was achieved by RNA interference (RNAi), targeting the telomerase reverse transcriptase (TERT) subunits of telomerase. Transfection of TERT siRNA downregulates TERT gene expression and induced downregulation of telomerase activity. Investigation of the effect of silencing TERT in telomerase was further validated through proteomic analysis by performing 2-dimension electrophoresis (2DE) coupled with MALDI-TOF/TOF. 12 protein spots in HeLa cells were reported to be significantly differentially expressed with 11 of them were upregulated and 1 downregulated. Through STRING analysis, differentially expressed proteins demonstrated strong associations with endoplasmic reticulum stress marker and mitochondrial energy production marker. In conclusions, the result exhibited novel integrated proteomic response involving endoplasmic reticulum stress and mitochondrial energy production in response to the TERT downregulation in cervical cancer cells.
    Matched MeSH terms: RNA Interference*
  11. Lim MP, Firdaus-Raih M, Nathan S
    Front Microbiol, 2016;7:1436.
    PMID: 27672387 DOI: 10.3389/fmicb.2016.01436
    Burkholderia pseudomallei, the causative agent of melioidosis, is among a growing number of bacterial pathogens that are increasingly antibiotic resistant. Antimicrobial peptides (AMPs) have been investigated as an alternative approach to treat microbial infections, as generally, there is a lower likelihood that a pathogen will develop resistance to AMPs. In this study, 36 candidate Caenorhabditis elegans genes that encode secreted peptides of <150 amino acids and previously shown to be overexpressed during infection by B. pseudomallei were identified from the expression profile of infected nematodes. RNA interference (RNAi)-based knockdown of 12/34 peptide-encoding genes resulted in enhanced nematode susceptibility to B. pseudomallei without affecting worm fitness. A microdilution test demonstrated that two peptides, NLP-31 and Y43C5A.3, exhibited anti-B. pseudomallei activity in a dose dependent manner on different pathogens. Time kill analysis proposed that these peptides were bacteriostatic against B. pseudomallei at concentrations up to 8× MIC90. The SYTOX green assay demonstrated that NLP-31 and Y43C5A.3 did not disrupt the B. pseudomallei membrane. Instead, gel retardation assays revealed that both peptides were able to bind to DNA and interfere with bacterial viability. In parallel, microscopic examination showed induction of cellular filamentation, a hallmark of DNA synthesis inhibition, of NLP-31 and Y43C5A.3 treated cells. In addition, the peptides also regulated the expression of inflammatory cytokines in B. pseudomallei infected macrophage cells. Collectively, these findings demonstrate the potential of NLP-31 and Y43C5A.3 as anti-B. pseudomallei peptides based on their function as immune modulators.
    Matched MeSH terms: RNA Interference
  12. Yeo KS, Tan MC, Wong WY, Loh SW, Lam YL, Tan CL, et al.
    Sci Rep, 2016 Sep 27;6:34125.
    PMID: 27671354 DOI: 10.1038/srep34125
    TNF-induced signaling mediates pleiotropic biological consequences including inflammation, immunity, cell proliferation and apoptosis. Misregulation of TNF signaling has been attributed as a major cause of chronic inflammatory diseases and cancer. Jumonji domain-containing protein 8 (JMJD8) belongs to the JmjC family. However, only part of the family members has been described as hydroxylase enzymes that function as histone demethylases. Here, we report that JMJD8 positively regulates TNF-induced NF-κB signaling. Silencing the expression of JMJD8 using RNA interference (RNAi) greatly suppresses TNF-induced expression of several NF-κB-dependent genes. Furthermore, knockdown of JMJD8 expression reduces RIP ubiquitination, IKK kinase activity, delays IκBα degradation and subsequently blocks nuclear translocation of p65. In addition, JMJD8 deficiency enhances TNF-induced apoptosis. Taken together, these findings indicate that JMJD8 functions as a positive regulator of TNF-induced NF-κB signaling.
    Matched MeSH terms: RNA Interference
  13. Dua K, Wadhwa R, Singhvi G, Rapalli V, Shukla SD, Shastri MD, et al.
    Drug Dev Res, 2019 09;80(6):714-730.
    PMID: 31691339 DOI: 10.1002/ddr.21571
    Lung diseases are the leading cause of mortality worldwide. The currently available therapies are not sufficient, leading to the urgent need for new therapies with sustained anti-inflammatory effects. Small/short or silencing interfering RNA (siRNA) has potential therapeutic implications through post-transcriptional downregulation of the target gene expression. siRNA is essential in gene regulation, so is more favorable over other gene therapies due to its small size, high specificity, potency, and no or low immune response. In chronic respiratory diseases, local and targeted delivery of siRNA is achieved via inhalation. The effectual delivery can be attained by the generation of aerosols via inhalers and nebulizers, which overcomes anatomical barriers, alveolar macrophage clearance and mucociliary clearance. In this review, we discuss the different siRNA nanocarrier systems for chronic respiratory diseases, for safe and effective delivery. siRNA mediated pro-inflammatory gene or miRNA targeting approach can be a useful approach in combating chronic respiratory inflammatory conditions and thus providing sustained drug delivery, reduced therapeutic dose, and improved patient compliance. This review will be of high relevance to the formulation, biological and translational scientists working in the area of respiratory diseases.
    Matched MeSH terms: RNA Interference
  14. M.R. Mohd Hafiz, M.Z. Mazatulikhma, F.A. Mohd Faiz, M.S. Mohamed Saifulaman
    Sains Malaysiana, 2013;42:1131-1137.
    In this study, RNA interference (RNAi) was carried out as an experimental technique to knockdown three mitogen-activated protein kinase (MAPK) pathway genes, raf-1, mekk1 and mlk3 in acute myeloid leukemia (AML) cells. Conventionally, RNAi knockdown experiments target a single gene for functional studies or therapeutic purposes. We wanted to explore the potential differences or similarities between targeting single targets or multiple target genes in a single application. We achieved knockdown of gene expression levels of between 40 and 60% for the RNAi experiments, with better knockdown observed in single target gene experiments in comparison with the multiple target gene experiment. Microarray analysis indicated that the transfection process had most likely induced the immune response from the cells in every RNAi treatment. This might indicate that when the MAPK signaling pathway is partially blocked, in tandem with the immune response, the cells will begin signaling for apoptosis leading to cellular death of the leukemic cells.
    Matched MeSH terms: RNA Interference
  15. Samad MA, Saiman MZ, Abdul Majid N, Karsani SA, Yaacob JS
    Cell Biochem Biophys, 2024 Mar;82(1):153-173.
    PMID: 38198024 DOI: 10.1007/s12013-023-01210-8
    Colorectal cancer (CRC) is the most common cancer in both men and women and is associated with increased telomerase levels and activity. The potential downstream effects of TERT and/or TERC downregulation by berberine (a telomerase inhibitor) or RNA interference (RNAi) on various target RNAs, proteins, relative telomerase activity (RTA), relative telomere length (RTL), hydrogen peroxide concentration [H2O2], percentage of cell cycle distribution, cell size and granularity as well as cellular metabolites were explored in HCT 116 cell line. Knockdown of TERT decreased TERC. The downregulation of TERT and/or TERC caused increment of [H2O2], G0/G1 phase arrest in addition to decreased S and G2/M phases, as well as diminished cell size. RTL was later reduced as a result of TERT, TERT and/or TERC downregulation which decreased RTA. It was discovered that xanthine oxidase (XO) was significantly and positively correlated at FDR-adjusted p value RNAs, proteins, metabolites, oxidative stress mechanism and subsequently phenotypic changes in HCT 116 which is valuable to understand the intricate biological interactions and mechanism of telomerase in CRC.
    Matched MeSH terms: RNA Interference
  16. Alhoot MA, Wang SM, Sekaran SD
    PLoS Negl Trop Dis, 2011 Nov;5(11):e1410.
    PMID: 22140591 DOI: 10.1371/journal.pntd.0001410
    Dengue infection ranks as one of the most significant viral diseases of the globe. Currently, there is no specific vaccine or antiviral therapy for prevention or treatment. Monocytes/macrophages are the principal target cells for dengue virus and are responsible for disseminating the virus after its transmission. Dengue virus enters target cells via receptor-mediated endocytosis after the viral envelope protein E attaches to the cell surface receptor. This study aimed to investigate the effect of silencing the CD-14 associated molecule and clathrin-mediated endocytosis using siRNA on dengue virus entry into monocytes.
    Matched MeSH terms: RNA Interference*
  17. Liew K, Yu GQS, Wei Pua LJ, Wong LZ, Tham SY, Hii LW, et al.
    Cancer Lett, 2021 Apr 28;504:81-90.
    PMID: 33587980 DOI: 10.1016/j.canlet.2021.02.006
    Despite recent in advances in the management of nasopharyngeal carcinoma (NPC), development of targeted therapy remains challenging particularly in patients with recurrent or metastatic disease. To search for clinically relevant targets for the treatment of NPC, we carried out parallel genome-wide functional screens to identified essential genes that are required for NPC cells proliferation and cisplatin resistance. We identified lymphocyte-specific protein tyrosine kinase (LCK) as a key vulnerability of both proliferation and cisplatin resistance. Depletion of endogenous LCK or treatment of cells with LCK inhibitor induced tumor-specific cell death and synergized cisplatin sensitivity in EBV-positive C666-1 and EBV-negative SUNE1 cells. Further analyses demonstrated that LCK is regulating the proliferation and cisplatin resistance through activation of signal transducer and activator of transcription 5 (STAT5). Taken together, our study provides a molecular basis for targeting LCK and STAT5 signaling as potential druggable targets for the management of NPC.
    Matched MeSH terms: RNA Interference*
  18. Tiwari GJ, Liu Q, Shreshtha P, Li Z, Rahman S
    BMC Plant Biol, 2016 08 31;16(1):189.
    PMID: 27581494 DOI: 10.1186/s12870-016-0881-6
    BACKGROUND: The bran from polished rice grains can be used to produce rice bran oil (RBO). High oleic (HO) RBO has been generated previously through RNAi down-regulation of OsFAD2-1. HO-RBO has higher oxidative stability and could be directly used in the food industry without hydrogenation, and is hence free of trans fatty acids. However, relative to a classic oilseed, lipid metabolism in the rice grain is poorly studied and the genetic alteration in the novel HO genotype remains unexplored.

    RESULTS: Here, we have undertaken further analysis of role of OsFAD2-1 in the developing rice grain. The use of Illumina-based NGS transcriptomics analysis of developing rice grain reveals that knockdown of Os-FAD2-1 gene expression was accompanied by the down regulation of the expression of a number of key genes in the lipid biosynthesis pathway in the HO rice line. A slightly higher level of oil accumulation was also observed in the HO-RBO.

    CONCLUSION: Prominent among the down regulated genes were those that coded for FatA, LACS, SAD2, SAD5, caleosin and steroleosin. It may be possible to further increase the oleic acid content in rice oil by altering the expression of the lipid biosynthetic genes that are affected in the HO line.

    Matched MeSH terms: RNA Interference*
  19. Behboodian B, Mohd Ali Z, Ismail I, Zainal Z
    ScientificWorldJournal, 2012;2012:439870.
    PMID: 22919320 DOI: 10.1100/2012/439870
    The plant hormone, ethylene, is an important regulator which involved in regulating fruit ripening and flower senescence. In this study, RNA interference (RNAi) technology was employed to silence the genes involved in ethylene biosynthetic pathway. This was achieved by blocking the expression of specific gene encoding the ACC oxidase. Initially, cDNA corresponding to ACO1 of lowland tomato cultivar (MT1), which has high identity with ACO1 of Solanum lycopersicum in GenBank, was cloned through RT-PCR. Using a partial coding region of ACO1, one hpRNAi transformation vector was constructed and expressed ectopically under the 35S promoter. Results showed that transgenic lines harboring the hpRNA-ACO1 construct had lower ethylene production and a longer shelf life of 32 days as compared to 10 days for wild-type fruits. Changes in cell wall degrading enzyme activities were also investigated in cases where the transgenic fruits exhibited reduced rates of firmness loss, which can be associated with a decrease in pectin methylesterase (PME) and polygalacturonase (PG) activities. However, no significant change was detected in both transgenic and wild-type fruits in terms of β-galactosidase (β-Gal) activity and levels of total soluble solid, titratable acid and ascorbic acid.
    Matched MeSH terms: RNA Interference*
  20. Tekade RK, Maheshwari RG, Sharma PA, Tekade M, Chauhan AS
    Curr Pharm Des, 2015;21(31):4614-36.
    PMID: 26486147
    siRNA technology presents a helpful means of gene silencing in mammalian cells. Advancement in the field includes enhanced attentiveness in the characterization of target and off-target effects employing suitable controls and gene expression microarrays. These will permit expansion in the measurement of single and multiple target combinations and also permit comprehensive efforts to understand mammalian cell processes. Another fact is that the delivery of siRNA requires the creation of a nanoparticulate vector with controlled structural geometry and surface modalities inside the targeted cells. On the other hand, dendrimers represent the class of carrier system where massive control over size, shape and physicochemical properties makes this delivery vector exceptional and favorable in genetic transfection applications. The siRNA therapeutics may be incorporated inside the geometry of the density controlled dendrimers with the option of engineering the structure to the specific needs of the genetic material and its indication. The existing reports on the siRNA carrying and deliverance potential of dendrimers clearly suggest the significance of this novel class of polymeric architecture and certainly elevate the futuristic use of this highly branched vector as genetic material delivery system.
    Matched MeSH terms: RNA Interference
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