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Nanoparticle-mediated delivery of therapeutic genes: focus on miRNA therapeutics
Muthiah, Muthunarayanan,Park, In-Kyu,Cho, Chong-Su Informa UK, Ltd. 2013 Expert opinion on drug delivery Vol.10 No.9
<P><B><I>Introduction:</I></B> Micro RNAs (miRNA) are 21 - 23 nucleotides long and regulate the expression of coding genes by binding imperfectly with their 3′ UTR region. The miRNA profile is altered in pathological processes, making miRNAs good targets for drug therapy. Restoration of down-regulated miRNA or inhibition of overexpressed miRNA to return miRNA to its normal state is the basis of miRNA-based therapy. This review focuses on nanocarriers used for the delivery of miRNA that confer physical stability to the unstable RNA structure, protect the RNA from nuclease degradation and aid in effective silencing of target genes.</P><P><B><I>Areas covered:</I></B> The necessity of the nanocarrier for the delivery of the miRNA is emphasized and the recent research on liposome-, metal- and polymer-mediated miRNA delivery for the inhibition or replacement of the disease-related miRNA is summarized.</P><P><B><I>Expert opinion:</I></B> The size, charge and surface properties of nanocarriers have to be tuned to ensure effective and safe delivery of the miRNA in clinical practice. The immune responses related to the nanocarriers and the double-stranded nucleotide delivery remain to be addressed. Also, the binding of miRNAs to non-specific targets has to be studied in more detail because miRNAs have multiple targets due to partial binding unlike siRNA.</P>
Muthiah, M.,Che, H.L.,Kalash, S.,Jo, J.,Choi, S.Y.,Kim, W.J.,Cho, C.S.,Lee, J.Y.,Park, I.K. Elsevier 2015 Colloids and surfaces. B, Biointerfaces Vol.126 No.-
<P>In this study, thiol-modified siRNA (SH-siRNA) was delivered by bioreducible polyethylenimine (ssPEI), to enhance physicochemical properties of polyplexes and function of siRNA through disulfide bonding between SH-siRNA and ssPEI. The ssPEI was utilized to deliver Akt1 SH-siRNA for suppression of Akt1 mRNA and blockage of Akt1 protein translation, resulting in reduced cellular proliferation and the induction of apoptosis. Disulfide bondings between the ssPEI and SH-siRNA through thiol groups in both were confirmed by DTT treatment. Complexation between ssPEI and Akt1SH-siRNA was enhanced and reduced surface charge of ssPEI/Akt1SH-siRNA complexes with smaller average particle sizes even at lower N/P ratios was obtained compared with PEI/Akt1siRNA ones. Cellular uptake of ssPEI/Akt1SH-siRNA complexes in CT-26 mouse colon cancer cells was also enhanced. The ssPEI/Akt1SH-siRNA complexes reduced proliferation and increased apoptosis of mouse colon cancer cells in vitro. In an in vivo mouse tumor model, the complexes reduced tumor proliferation and downregulation of Akt1 compared to controls. (C) 2014 Elsevier B.V. All rights reserved.</P>
Largia Muthiah Joe Virgin,Pandian Subramani,Shilpha Jayabalan,Chitradevi Muniyarajan,Kavikkuil Manickam,Sohn Soo In,Ramesh Manikandan 한국식물생명공학회 2022 Plant biotechnology reports Vol.16 No.6
Justicia gendarussa Burm. f. is an indispensable medicinal plant owing to its abundance of phytoconstituents and medicinal uses. In the study, we demonstrated the successful in vitro regeneration of J. gendarussa through nodal explants and its genetic and phytochemical analysis. A combination of 2 mg L-1 BA + 0.1 mg L-1 NAA + 15 mg L-1 spermidine was found to be reliable in producing the maximum number of multiple shoots (16.6) and vigorous roots in Murashige and Skoog medium. Rooted shoots have been efciently hardened and then slowly acclimatized to natural conditions. SPAR-based genetic fdelity checking revealed the true-to-type nature of in vitro regenerated plants with little variations by generating 105 bands through amplifcation of 15 primers. Furthermore, the protocol followed for in vitro culture was strengthened by the comparative determination of Total Phenolic Content (TPC), Total Flavonoid Content (TFC), and Antioxidant Potential (AP). Methanolic extracts of in vitro plants showed higher amounts of TPC, TFC, and AP when compared to in vivo plants which might be due to the infuence of plant growth hormones. Thus the in vitro regeneration protocol derived would vitally expedite large scale production of true to type plantlets of J. gendarussa. In addition, an attempt was made for the frst time to devise a suitable protocol for the induction of hairy roots from this plant using two Agrobacterium rhizogenes strains which would lead to enhanced production of important anti-HIV metabolites of the plant such as gendarussin A, B and so on.