scholarly journals RNA nanotechnology for computer design and in vivo computation

2013 ◽  
Vol 371 (2000) ◽  
pp. 20120310 ◽  
Author(s):  
Meikang Qiu ◽  
Emil Khisamutdinov ◽  
Zhengyi Zhao ◽  
Cheryl Pan ◽  
Jeong-Woo Choi ◽  
...  
Keyword(s):  
Self Assembly ◽  
Acid Resistance ◽  
Computational Design ◽  
Computer Design ◽  
Property A ◽  
Rna Sequences ◽  
Rna Nanotechnology ◽  
Molecular Scale ◽  
Computer Scientists

Molecular-scale computing has been explored since 1989 owing to the foreseeable limitation of Moore's law for silicon-based computation devices. With the potential of massive parallelism, low energy consumption and capability of working in vivo , molecular-scale computing promises a new computational paradigm. Inspired by the concepts from the electronic computer, DNA computing has realized basic Boolean functions and has progressed into multi-layered circuits. Recently, RNA nanotechnology has emerged as an alternative approach. Owing to the newly discovered thermodynamic stability of a special RNA motif (Shu et al. 2011 Nat. Nanotechnol. 6 , 658–667 ( doi:10.1038/nnano.2011.105 )), RNA nanoparticles are emerging as another promising medium for nanodevice and nanomedicine as well as molecular-scale computing. Like DNA, RNA sequences can be designed to form desired secondary structures in a straightforward manner, but RNA is structurally more versatile and more thermodynamically stable owing to its non-canonical base-pairing, tertiary interactions and base-stacking property. A 90-nucleotide RNA can exhibit 4 90 nanostructures, and its loops and tertiary architecture can serve as a mounting dovetail that eliminates the need for external linking dowels. Its enzymatic and fluorogenic activity creates diversity in computational design. Varieties of small RNA can work cooperatively, synergistically or antagonistically to carry out computational logic circuits. The riboswitch and enzymatic ribozyme activities and its special in vivo attributes offer a great potential for in vivo computation. Unique features in transcription, termination, self-assembly, self-processing and acid resistance enable in vivo production of RNA nanoparticles that harbour various regulators for intracellular manipulation. With all these advantages, RNA computation is promising, but it is still in its infancy. Many challenges still exist. Collaborations between RNA nanotechnologists and computer scientists are necessary to advance this nascent technology.

In vitro and in vivo polysaccharides assembly: ultrastructural and cytochemical study of growing plant cell wall components.

1978 ◽  
Vol 36 (2) ◽  
pp. 434-435
Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland
Keyword(s):  
Cell Wall ◽  
Self Assembly ◽  
Plant Cell Wall ◽  
Higher Plants ◽  
Three Dimensional ◽  
Cytochemical Study ◽  
Wall Components

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.

Programmable in vitro Co-Encapsidation of Guest Proteins Inside Protein Nanocages

2018 ◽  
Author(s):  
Noor H. Dashti ◽  
Rufika S. Abidin ◽  
Frank Sainsbury
Keyword(s):  
Self Assembly ◽  
Mammalian Cells ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Super Resolution ◽  
Cell Engineering ◽  
Particle Analysis ◽  
Protein Cages

Bioinspired self-sorting and self-assembling systems using engineered versions of natural protein cages have been developed for biocatalysis and therapeutic delivery. The packaging and intracellular delivery of guest proteins is of particular interest for both <i>in vitro</i> and <i>in vivo</i> cell engineering. However, there is a lack of platforms in bionanotechnology that combine programmable guest protein encapsidation with efficient intracellular uptake. We report a minimal peptide anchor for <i>in vivo</i> self-sorting of cargo-linked capsomeres of the Murine polyomavirus (MPyV) major coat protein that enables controlled encapsidation of guest proteins by <i>in vitro</i> self-assembly. Using Förster resonance energy transfer (FRET) we demonstrate the flexibility in this system to support co-encapsidation of multiple proteins. Complementing these ensemble measurements with single particle analysis by super-resolution microscopy shows that the stochastic nature of co-encapsidation is an overriding principle. This has implications for the design and deployment of both native and engineered self-sorting encapsulation systems and for the assembly of infectious virions. Taking advantage of the encoded affinity for sialic acids ubiquitously displayed on the surface of mammalian cells, we demonstrate the ability of self-assembled MPyV virus-like particles to mediate efficient delivery of guest proteins to the cytosol of primary human cells. This platform for programmable co-encapsidation and efficient cytosolic delivery of complementary biomolecules therefore has enormous potential in cell engineering.

scholarly journals Development of In Situ Self-Assembly Nanoparticles to Encapsulate Lopinavir and Ritonavir for Long-Acting Subcutaneous Injection

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 904
Author(s):  
Irin Tanaudommongkon ◽  
Asama Tanaudommongkon ◽  
Xiaowei Dong
Keyword(s):  
Sustained Release ◽  
Trough Concentration ◽  
Self Assembly ◽  
Subcutaneous Injection ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Long Acting

Most antiretroviral medications for human immunodeficiency virus treatment and prevention require high levels of patient adherence, such that medications need to be administered daily without missing doses. Here, a long-acting subcutaneous injection of lopinavir (LPV) in combination with ritonavir (RTV) using in situ self-assembly nanoparticles (ISNPs) was developed to potentially overcome adherence barriers. The ISNP approach can improve the pharmacokinetic profiles of the drugs. The ISNPs were characterized in terms of particle size, drug entrapment efficiency, drug loading, in vitro release study, and in vivo pharmacokinetic study. LPV/RTV ISNPs were 167.8 nm in size, with a polydispersity index of less than 0.35. The entrapment efficiency was over 98% for both LPV and RTV, with drug loadings of 25% LPV and 6.3% RTV. A slow release rate of LPV was observed at about 20% on day 5, followed by a sustained release beyond 14 days. RTV released faster than LPV in the first 5 days and slower than LPV thereafter. LPV trough concentration remained above 160 ng/mL and RTV trough concentration was above 50 ng/mL after 6 days with one subcutaneous injection. Overall, the ISNP-based LPV/RTV injection showed sustained release profiles in both in vitro and in vivo studies.

scholarly journals Force generation by protein–DNA co-condensation

2021 ◽  
Author(s):  
Thomas Quail ◽  
Stefan Golfier ◽  
Maria Elsner ◽  
Keisuke Ishihara ◽  
Vasanthanarayan Murugesan ◽  
...  
Keyword(s):  
Optical Tweezers ◽  
Self Assembly ◽  
Spider Silk ◽  
Regulatory Elements ◽  
Heterochromatin Formation ◽  
First Order Phase Transition ◽  
Dna Strand ◽  
First Order Phase

AbstractInteractions between liquids and surfaces generate forces1,2 that are crucial for many processes in biology, physics and engineering, including the motion of insects on the surface of water3, modulation of the material properties of spider silk4 and self-assembly of microstructures5. Recent studies have shown that cells assemble biomolecular condensates via phase separation6. In the nucleus, these condensates are thought to drive transcription7, heterochromatin formation8, nucleolus assembly9 and DNA repair10. Here we show that the interaction between liquid-like condensates and DNA generates forces that might play a role in bringing distant regulatory elements of DNA together, a key step in transcriptional regulation. We combine quantitative microscopy, in vitro reconstitution, optical tweezers and theory to show that the transcription factor FoxA1 mediates the condensation of a protein–DNA phase via a mesoscopic first-order phase transition. After nucleation, co-condensation forces drive growth of this phase by pulling non-condensed DNA. Altering the tension on the DNA strand enlarges or dissolves the condensates, revealing their mechanosensitive nature. These findings show that DNA condensation mediated by transcription factors could bring distant regions of DNA into close proximity, suggesting that this physical mechanism is a possible general regulatory principle for chromatin organization that may be relevant in vivo.

scholarly journals Next generation polyphosphazene immunoadjuvant: Synthesis, self-assembly and in vivo potency with human papillomavirus VLPs-based vaccine

2021 ◽  
Vol 33 ◽  
pp. 102359
Author(s):  
Alexander Marin ◽  
Ananda Chowdhury ◽  
Sarah M. Valencia ◽  
Athina Zacharia ◽  
Reinhard Kirnbauer ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Self Assembly ◽  
Next Generation

scholarly journals De novo design of self-assembling helical protein filaments

Science ◽  
2018 ◽  
Vol 362 (6415) ◽  
pp. 705-709 ◽  
Author(s):  
Hao Shen ◽  
Jorge A. Fallas ◽  
Eric Lynch ◽  
William Sheffler ◽  
Bradley Parry ◽  
...  
Keyword(s):  
De Novo ◽  
Computational Design ◽  
Building Blocks ◽  
Repeat Units ◽  
Self Assembling ◽  
Wide Range ◽  
Helical Protein ◽  
Monomeric Proteins

We describe a general computational approach to designing self-assembling helical filaments from monomeric proteins and use this approach to design proteins that assemble into micrometer-scale filaments with a wide range of geometries in vivo and in vitro. Cryo–electron microscopy structures of six designs are close to the computational design models. The filament building blocks are idealized repeat proteins, and thus the diameter of the filaments can be systematically tuned by varying the number of repeat units. The assembly and disassembly of the filaments can be controlled by engineered anchor and capping units built from monomers lacking one of the interaction surfaces. The ability to generate dynamic, highly ordered structures that span micrometers from protein monomers opens up possibilities for the fabrication of new multiscale metamaterials.

scholarly journals Dissecting the Structure-Function Relationship of a Fungicidal Peptide Derived from the Constant Region of Human Immunoglobulins

2016 ◽  
Vol 60 (4) ◽  
pp. 2435-2442 ◽  
Author(s):  
Tecla Ciociola ◽  
Thelma A. Pertinhez ◽  
Laura Giovati ◽  
Martina Sperindè ◽  
Walter Magliani ◽  
...  
Keyword(s):  
Self Assembly ◽  
Galleria Mellonella ◽  
Critical Role ◽  
Yeast Cells ◽  
Therapeutic Effects ◽  
Constant Region ◽  
Content Type ◽  
Complementarity Determining Regions

ABSTRACTSynthetic peptides encompassing sequences related to the complementarity-determining regions of antibodies or derived from their constant region (Fc peptides) were proven to exert differential antimicrobial, antiviral, antitumor, and/or immunomodulatory activitiesin vitroand/orin vivo, regardless of the specificity and isotype of the parental antibody. Alanine substitution derivatives of these peptides exhibited unaltered, increased, or decreased candidacidal activitiesin vitro. The bioactive IgG-derived Fc N10K peptide (NQVSLTCLVK) spontaneously self-assembles, a feature previously recognized as relevant for the therapeutic activity of another antibody-derived peptide. We evaluated the contribution of each residue to the peptide self-assembling capability by circular-dichroism spectroscopy. The interaction of the N10K peptide and its derivatives withCandida albicanscells was studied by confocal, transmission, and scanning electron microscopy. The apoptosis and autophagy induction profiles in yeast cells treated with the peptides were evaluated by flow cytometry, and the therapeutic efficacy against candidal infection was studied in aGalleria mellonellamodel. Overall, the results indicate a critical role for some residues in the self-assembly process and a correlation of that capability with the candidacidal activities of the peptidesin vitroand their therapeutic effectsin vivo.

scholarly journals Dual Targeting of Cancer Cells and MMPs with Self-Assembly Hybrid Nanoparticles for Combination Therapy in Combating Cancer

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 1990
Author(s):  
Kai Zhang ◽  
Jingjing Li ◽  
Xiaofei Xin ◽  
Xiaoqing Du ◽  
Di Zhao ◽  
...  
Keyword(s):  
T Cells ◽  
Cancer Cells ◽  
Self Assembly ◽  
Chemotherapeutic Agents ◽  
Hybrid Nanoparticles ◽  
Control Group ◽  
Hyperthermia Treatment ◽  
Immune Modulators ◽  
Dual Targeting

The co-delivery of chemotherapeutic agents and immune modulators to their targets remains to be a great challenge for nanocarriers. Here, we developed a hybrid thermosensitive nanoparticle (TMNP) which could co-deliver paclitaxel-loaded transferrin (PTX@TF) and marimastat-loaded thermosensitive liposomes (MMST/LTSLs) for the dual targeting of cancer cells and the microenvironment. TMNPs could rapidly release the two payloads triggered by the hyperthermia treatment at the site of tumor. The released PTX@TF entered cancer cells via transferrin-receptor-mediated endocytosis and inhibited the survival of tumor cells. MMST was intelligently employed as an immunomodulator to improve immunotherapy by inhibiting matrix metalloproteinases to reduce chemokine degradation and recruit T cells. The TMNPs promoted the tumor infiltration of CD3+ T cells by 2-fold, including memory/effector CD8+ T cells (4.2-fold) and CD4+ (1.7-fold), but not regulatory T cells. Our in vivo anti-tumor experiment suggested that TMNPs possessed the highest tumor growth inhibitory rate (80.86%) compared with the control group. We demonstrated that the nanoplatform could effectively inhibit the growth of tumors and enhance T cell recruitment through the co-delivery of paclitaxel and marimastat, which could be a promising strategy for the combination of chemotherapy and immunotherapy for cancer treatment.

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