scholarly journals Signal responsive transient coacervation in complex coacervate core micelles

2021 ◽  
Author(s):  
Reece W. Lewis ◽  
Benjamin Klemm ◽  
Mariano Macchione ◽  
Rienk Eelkema
Keyword(s):  
Nucleic Acid ◽  
Block Copolymers ◽  
Tertiary Amine ◽  
Salt Concentration ◽  
Reaction Network ◽  
Material Design ◽  
Nucleic Acid Delivery ◽  
Complex Coacervate ◽  
Complex Coacervate Core Micelles ◽  
Coacervate Phase

Triggered coacervate phase (de)stabilisation in complex coacervate core micelles (C3Ms) has traditionally been limited to changes in pH and salt concentration, limiting options in responsive C3M material design. To expand this toolbox, we have developed C3Ms, that, at constant physiological pH, assemble and disassemble by coupling to a chemical reaction network (CRN) driven by the conversion of electron deficient allyl acetates and thiol or amine nucleophiles. This CRN produces transient quaternization of tertiary amine-functionalised block copolymers, which can then form the complex coacervate phase. We demonstrate triggered C3M assembly using two different allyl acetates, resulting in dramatically different assembly rates from hours to days. These are applied in various combinations with selected nucleophiles, demonstrating sequential signal induced C3M formation and deformation, as well as transient non-equilibrium (de)formation. We expect that timed and signal-responsive control over coacervate phase formation at physiological pH will find application in nucleic acid delivery, nano reactors and protocell research.

scholarly journals Signal responsive transient coacervation in complex coacervate core micelles

2021 ◽  
Author(s):  
Reece W. Lewis ◽  
Benjamin Klemm ◽  
Mariano Macchione ◽  
Rienk Eelkema
Keyword(s):  
Nucleic Acid ◽  
Block Copolymers ◽  
Tertiary Amine ◽  
Salt Concentration ◽  
Reaction Network ◽  
Material Design ◽  
Nucleic Acid Delivery ◽  
Complex Coacervate ◽  
Complex Coacervate Core Micelles ◽  
Coacervate Phase

Triggered coacervate phase (de)stabilisation in complex coacervate core micelles (C3Ms) has traditionally been limited to changes in pH and salt concentration, limiting options in responsive C3M material design. To expand this toolbox, we have developed C3Ms, that, at constant physiological pH, assemble and disassemble by coupling to a chemical reaction network (CRN) driven by the conversion of electron deficient allyl acetates and thiol or amine nucleophiles. This CRN produces transient quaternization of tertiary amine-functionalised block copolymers, which can then form the complex coacervate phase. We demonstrate triggered C3M assembly using two different allyl acetates, resulting in dramatically different assembly rates from hours to days. These are applied in various combinations with selected nucleophiles, demonstrating sequential signal induced C3M formation and deformation, as well as transient non-equilibrium (de)formation. We expect that timed and signal-responsive control over coacervate phase formation at physiological pH will find application in nucleic acid delivery, nano reactors and protocell research.

scholarly journals Noncationic Material Design for Nucleic Acid Delivery

2020 ◽  
Vol 3 (3) ◽  
pp. 1900206 ◽  
Author(s):  
Ziwen Jiang ◽  
S. Thayumanavan
Keyword(s):  
Nucleic Acid ◽  
Material Design ◽  
Nucleic Acid Delivery

Non-Viral Nucleic Acid Delivery: Key Challenges and Future Directions

2011 ◽  
Vol 8 (3) ◽  
pp. 235-244 ◽  
Author(s):  
Mahmoud Elsabahy ◽  
Adil Nazarali ◽  
Marianna Foldvari
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acid Delivery ◽  
Viral Nucleic Acid ◽  
Future Directions

scholarly journals A CRISPR-Cas autocatalysis-driven feedback amplification network for supersensitive DNA diagnostics

2021 ◽  
Vol 7 (5) ◽  
pp. eabc7802
Author(s):  
Kai Shi ◽  
Shiyi Xie ◽  
Renyun Tian ◽  
Shuo Wang ◽  
Qin Lu ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Genomic Dna ◽  
Reaction Network ◽  
Clinical Samples ◽  
Great Promise ◽  
Base Specificity ◽  
Nucleotide Mutation ◽  
Positive Feedback Circuit ◽  
Stringent Target ◽  
And Function

Artificial nucleic acid circuits with precisely controllable dynamic and function have shown great promise in biosensing, but their utility in molecular diagnostics is still restrained by the inability to process genomic DNA directly and moderate sensitivity. To address this limitation, we present a CRISPR-Cas–powered catalytic nucleic acid circuit, namely, CRISPR-Cas–only amplification network (CONAN), for isothermally amplified detection of genomic DNA. By integrating the stringent target recognition, helicase activity, and trans-cleavage activity of Cas12a, a Cas12a autocatalysis-driven artificial reaction network is programmed to construct a positive feedback circuit with exponential dynamic in CONAN. Consequently, CONAN achieves one-enzyme, one-step, real-time detection of genomic DNA with attomolar sensitivity. Moreover, CONAN increases the intrinsic single-base specificity of Cas12a, and enables the effective detection of hepatitis B virus infection and human bladder cancer–associated single-nucleotide mutation in clinical samples, highlighting its potential as a powerful tool for disease diagnostics.

Charge‐Conversion Strategies for Nucleic Acid Delivery

2021 ◽  
pp. 2011103
Author(s):  
Kingshuk Dutta ◽  
Ritam Das ◽  
Jewel Medeiros ◽  
Pintu Kanjilal ◽  
S. Thayumanavan
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acid Delivery

scholarly journals Synthetic Histidine-Rich Peptides Inhibit Candida Species and Other Fungi In Vitro: Role of Endocytosis and Treatment Implications

2006 ◽  
Vol 50 (8) ◽  
pp. 2797-2805 ◽  
Author(s):  
Jingsong Zhu ◽  
Paul W. Luther ◽  
Qixin Leng ◽  
A. James Mixson
Keyword(s):  
Nucleic Acid ◽  
Antifungal Activity ◽  
Antifungal Agents ◽  
Fungal Growth ◽  
Nucleic Acid Delivery ◽  
Histatin 5 ◽  
Ph Buffering ◽  
Endosomal Acidification

ABSTRACT A family of histidine-rich peptides, histatins, is secreted by the parotid gland in mammals and exhibits marked inhibitory activity against a number of Candida species. We were particularly interested in the mechanism by which histidine-rich peptides inhibit fungal growth, because our laboratory has synthesized a variety of such peptides for drug and nucleic acid delivery. In contrast to naturally occurring peptides that are linear, peptides made on synthesizers can be varied with respect to their degrees of branching. Using this technology, we explored whether histidine-lysine (HK) polymers of different complexities and degrees of branching affect the growth of several species of Candida. Polymers with higher degrees of branching were progressively more effective against Candida albicans, with the four-branched polymer, H2K4b, most effective. Furthermore, H2K4b accumulated efficiently in C. albicans, which may indicate its ability to transport other antifungal agents intracellularly. Although H2K4b had greater antifungal activity than histatin 5, their mechanisms were similar. Toxicity in C. albicans induced by histatin 5 or branched HK peptides was markedly reduced by 4,4′-diisothiocyanato-stilbene-2,2′-disulfonate, an inhibitor of anion channels. We also determined that bafilomycin A1, an inhibitor of endosomal acidification, significantly decreased the antifungal activity of H2K4b. This suggests that the pH-buffering and subsequent endosomal-disrupting properties of histidine-rich peptides have a role in their antifungal activity. Moreover, the ability of the histidine component of these peptides to disrupt endosomes, which allows their escape from the lysosomal pathway, may explain why these peptides are both effective antifungal agents and nucleic acid delivery carriers.

Nucleic acid delivery using magnetic nanoparticles: the Magnetofection™ technology

2011 ◽  
Vol 2 (4) ◽  
pp. 471-482 ◽  
Author(s):  
Nicolas Laurent ◽  
Cédric Sapet ◽  
Loic Le Gourrierec ◽  
Elodie Bertosio ◽  
Olivier Zelphati
Keyword(s):  
Magnetic Nanoparticles ◽  
Nucleic Acid ◽  
Nucleic Acid Delivery

Arginine-rich hydrophobic polyethylenimine: Potent agent with simple components for nucleic acid delivery

2013 ◽  
Vol 60 ◽  
pp. 18-27 ◽  
Author(s):  
Hamideh Parhiz ◽  
Maryam Hashemi ◽  
Arash Hatefi ◽  
Wayne Thomas Shier ◽  
Sara Amel Farzad ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acid Delivery
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