Application of Phi29 Motor pRNA for Targeted Therapeutic Delivery of siRNA Silencing Metallothionein-IIA and Survivin in Ovarian Cancers

Tarapore, Pheruza; Shu, Yi; Guo, Peixuan; Ho, Shuk‐Mei

doi:10.1038/mt.2010.243

Cited by 55 publications

(44 citation statements)

References 47 publications

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“…Due to its stability and self-assembling properties in vitro, pRNA has been used successfully as a scaffold in the rational design of functional RNA supramolecular structures (Chen et al 2000;Shu et al 2004Shu et al , 2011bShu et al , 2013Guo 2005;Guo et al 2005Guo et al , 2006Li et al 2009Li et al , 2015aTarapore et al 2011;Haque et al 2012;Khisamutdinov et al 2014). Compared to phi29 pRNA, the stabilities of other natural and mutated pRNA sequences remain relatively underexplored (Shu et al 2011a;Li et al 2015b).…”

Section: Future Improvements In Predicting Rna 3wj Stabilitiesmentioning

confidence: 99%

“…Recent studies have shown that the SF5 and M2 pRNAs have the highest propensities for in vitro self-assembly (Gu and Schroeder 2011;Hao and Kieft 2014). The shape, self-assembly properties, and stability of pRNA can be leveraged in the rational design of functional supramolecular structures, including polyvalent nanoscale delivery systems (Chen et al 2000;Shu et al 2004Shu et al , 2011bShu et al , 2013Guo 2005;Guo et al 2005Guo et al , 2006Li et al 2009Li et al , 2015aTarapore et al 2011;Haque et al 2012;Khisamutdinov et al 2014). However, an important consideration in the design of functional nanostructures is the stability of the pRNA "building block" (Shu et al 2011a;Li et al 2015a,b).…”

Section: Introductionmentioning

confidence: 99%

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Thermodynamic stabilities of three-way junction nanomotifs in prohead RNA

Hill

Schroeder

2017

RNA

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The thermodynamic stabilities of four natural prohead or packaging RNA (pRNA) three-way junction (3WJ) nanomotifs and seven phi29 pRNA 3WJ deletion mutant nanomotifs were investigated using UV optical melting on a three-component RNA system. Our data reveal that some pRNA 3WJs are more stable than the phi29 pRNA 3WJ. The stability of the 3WJ contributes to the unique self-assembly properties of pRNA. Thus, ultrastable pRNA 3WJ motifs suggest new scaffolds for pRNA-based nanotechnology. We present data demonstrating that pRNA 3WJs differentially respond to the presence of metal ions. A comparison of our data with free energies predicted by currently available RNA secondary structure prediction programs shows that these programs do not accurately predict multibranch loop stabilities. These results will expand the existing parameters used for RNA secondary structure prediction from sequence in order to better inform RNA structure-function hypotheses and guide the rational design of functional RNA supramolecular assemblies.

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Section: Future Improvements In Predicting Rna 3wj Stabilitiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Thermodynamic stabilities of three-way junction nanomotifs in prohead RNA

Hill

Schroeder

2017

RNA

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“…Recent crystal structures of an engineered phi29 pRNA (Ding et al 2011), and of an isolated phi29 pRNA three-way junction (lacking the kissing interactions) (Zhang et al 2013) provided additional details of the intermolecular and intramolecular interactions that are important within this specific pRNA species. The knowledge resulting from these diverse studies of the phi29 pRNA has led to its adaptation as a polyvalent delivery vector and it has been useful for various types of RNA engineering (Guo et al , 2006Li et al 2009;Wendell et al 2009;Shu et al 2011;Tarapore et al 2011;Ye et al 2012;Khisamutdinov et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Diverse self-association properties within a family of phage packaging RNAs

Yang

Kieft

2014

RNA

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The packaging RNA (pRNA) found in phi29 bacteriophage is an essential component of a molecular motor that packages the phage's DNA genome. The pRNA forms higher-order multimers by intermolecular "kissing" interactions between identical molecules. The phi29 pRNA is a proven building block for nanotechnology and a model to explore the rare phenomenon of naturally occurring RNA self-association. Although the self-association properties of the phi29 pRNA have been extensively studied and this pRNA is used in nanotechnology, the characteristics of phylogenetically related pRNAs with divergent sequences are comparatively underexplored. These diverse pRNAs may lend new insight into both the rules governing RNA self-association and for RNA engineering. Therefore, we used a combination of biochemical and biophysical methods to resolve ambiguities in the proposed secondary structures of pRNAs from M2, GA1, SF5, and B103 phage, and to discover that different naturally occurring pRNAs form multimers of different stoichiometry and thermostability. Indeed, the M2 pRNA formed multimers that were particularly thermostable and may be more useful than phi29 pRNA for many applications. To determine if diverse pRNA behaviors are conferred by different kissing loop sequences, we designed and tested chimeric RNAs based on our revised secondary structural models. We found that although the kissing loops are essential for self-association, the critical determinant of multimer stability and stoichiometry is likely the diverse three-way junctions found in these RNAs. Using known features of RNA three-way junctions and solved structures of phi29 pRNA's junction, we propose a model for how different junctions affect self-association.

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“…Previous reports indicate that the pRNA-siRNA chimera exerts the silencing function of siRNA effectively and that the silencing efficiency of this chimera is similar to or even better than that of free siRNA (Zhang et al, 2009;Tarapore et al, 2011). Similarly, the pRNA-aptamer chimera interacts with the specific receptor, as expected (Guo et al, 2005; Figure 6.…”

Section: Discussionmentioning

confidence: 99%

Bottom-up assembly of RNA nanoparticles containing phi29 motor pRNA to silence the asthma STAT5b gene

Qiu¹,

Peng²,

Shi³

et al. 2012

Genet. Mol. Res.

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ABSTRACT. Activation of the transcription factor signal transducer and activator of transcription 5b (STAT5b) is a key event in the development of asthma. The potent ability of small interfering RNA (siRNA) to inhibit the expression of STAT5b mRNA has provided a new class of therapeutics for asthma. However, efficient delivery of siRNAs remains a key obstacle to their successful application. A targeted intracellular delivery approach for siRNA to specific cell types would be highly desirable. We used packaging RNA (pRNA), a component of the bacteriophage phi29-packaging motor, to deliver STAT5b siRNA to asthmatic spleen lymphocytes. This pRNA was able to spontaneously carry siRNA/STAT5b and aptamer/CD4, which is a ligand to CD4 molecule. Based on RT-PCR data, the pRNA dimer effectively inhibited STAT5b gene mRNA expression of asthmatic spleen lymphocytes, without the need for additional transfections. We conclude that the pRNA dimer carrying both siRNA and aptamer can deliver functional siRNA to cells; possibly, the aptamer acts as a ligand to interact with specific receptors. The pRNAs were evaluated with a CCK-8 kit and were found to have little cytotoxicity. We conclude that ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 11 (3): 3236-3245 (2012) pRNA as a novel nanovehicle for therapy in asthma 3237pRNA as a novel nanovehicle for RNA worth further study.

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Application of Phi29 Motor pRNA for Targeted Therapeutic Delivery of siRNA Silencing Metallothionein-IIA and Survivin in Ovarian Cancers

Cited by 55 publications

References 47 publications

Thermodynamic stabilities of three-way junction nanomotifs in prohead RNA

Thermodynamic stabilities of three-way junction nanomotifs in prohead RNA

Diverse self-association properties within a family of phage packaging RNAs

Bottom-up assembly of RNA nanoparticles containing phi29 motor pRNA to silence the asthma STAT5b gene

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