scholarly journals Peptide-Assisted Nucleic Acid Delivery Systems on the Rise

2021 ◽  
Vol 22 (16) ◽  
pp. 9092
Author(s):  
Shabnam Tarvirdipour ◽  
Michal Skowicki ◽  
Cora-Ann Schoenenberger ◽  
Cornelia G. Palivan
Keyword(s):  
Nucleic Acid ◽  
Side Effects ◽  
Nucleic Acids ◽  
Delivery Systems ◽  
Inorganic Nanoparticles ◽  
Water Soluble ◽  
Nucleic Acid Delivery ◽  
Subcellular Organelles ◽  
Cell Internalization ◽  
Site Of Action

Concerns associated with nanocarriers’ therapeutic efficacy and side effects have led to the development of strategies to advance them into targeted and responsive delivery systems. Owing to their bioactivity and biocompatibility, peptides play a key role in these strategies and, thus, have been extensively studied in nanomedicine. Peptide-based nanocarriers, in particular, have burgeoned with advances in purely peptidic structures and in combinations of peptides, both native and modified, with polymers, lipids, and inorganic nanoparticles. In this review, we summarize advances on peptides promoting gene delivery systems. The efficacy of nucleic acid therapies largely depends on cell internalization and the delivery to subcellular organelles. Hence, the review focuses on nanocarriers where peptides are pivotal in ferrying nucleic acids to their site of action, with a special emphasis on peptides that assist anionic, water-soluble nucleic acids in crossing the membrane barriers they encounter on their way to efficient function. In a second part, we address how peptides advance nanoassembly delivery tools, such that they navigate delivery barriers and release their nucleic acid cargo at specific sites in a controlled fashion.

scholarly journals Viral Mimicry as a Design Template for Nucleic Acid Nanocarriers

2021 ◽  
Vol 9 ◽  
Author(s):  
Ina F. de la Fuente ◽  
Shraddha S. Sawant ◽  
Mark Q. Tolentino ◽  
Patrick M. Corrigan ◽  
Jessica L. Rouge
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Molecular Mechanisms ◽  
Transfection Efficiency ◽  
Delivery Systems ◽  
Endosomal Escape ◽  
Nucleic Acid Delivery ◽  
Metastable Structure ◽  
Oligonucleotide Delivery ◽  
Genome Protection

Therapeutic nucleic acids hold immense potential in combating undruggable, gene-based diseases owing to their high programmability and relative ease of synthesis. While the delivery of this class of therapeutics has successfully entered the clinical setting, extrahepatic targeting, endosomal escape efficiency, and subcellular localization. On the other hand, viruses serve as natural carriers of nucleic acids and have acquired a plethora of structures and mechanisms that confer remarkable transfection efficiency. Thus, understanding the structure and mechanism of viruses can guide the design of synthetic nucleic acid vectors. This review revisits relevant structural and mechanistic features of viruses as design considerations for efficient nucleic acid delivery systems. This article explores how viral ligand display and a metastable structure are central to the molecular mechanisms of attachment, entry, and viral genome release. For comparison, accounted for are details on the design and intracellular fate of existing nucleic acid carriers and nanostructures that share similar and essential features to viruses. The review, thus, highlights unifying themes of viruses and nucleic acid delivery systems such as genome protection, target specificity, and controlled release. Sophisticated viral mechanisms that are yet to be exploited in oligonucleotide delivery are also identified as they could further the development of next-generation nonviral nucleic acid vectors.

Nucleic Acid Delivery System by the Combination of Lipid bubbles and Ultrasound

2018 ◽  
Vol 24 (23) ◽  
pp. 2673-2677 ◽  
Author(s):  
Yoko Endo-Takahashi ◽  
Kazuo Maruyama ◽  
Yoichi Negishi
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Delivery System ◽  
Target Genes ◽  
Delivery Systems ◽  
Target Site ◽  
Therapeutic Effects ◽  
Nucleic Acid Delivery ◽  
Clinical Implementation ◽  
Systemic Delivery

Background: RNA interference (RNAi)-based therapy has gained attention because of its potent genesilencing effect and high specificity. However, the efficient delivery of nucleic acids to the target site is a major challenge to the clinical implementation. Recently, ultrasound-mediated gene delivery systems have been developed and attracted interest due to its safety and site-specificity. By the combination with contrast agents, called microbubbles, not only the delivery effects but also the imaging effects are significantly enhanced. We developed lipid bubbles (LBs) entrapping an ultrasound contrast gas to enhance the efficacy of ultrasound-mediated delivery and imaging. In this review, we summarize ultrasound-mediated nucleic acid delivery systems and discuss the possibility of combining LBs and ultrasound for RNAi-based therapies. Methods: We prepared polyethylene glycol-modified liposomes and entrapped an echo-contrast gas within the liposomes. Small interfering RNA (siRNA) were transfected into cells and muscles using LBs and ultrasound. Moreover, we also developed nucleic acid-loaded LBs using cholesterol-conjugated siRNA or positively-charged lipid for an efficient systemic delivery of siRNA and microRNA. The usability of LBs for RNA delivery system was evaluated by the silencing effects of target genes and the therapeutic effects on ischemia hind limb. Results: A combination of LBs and therapeutic ultrasound was able to enhance the gene silencing effects by siRNA. Nucleic acid-loaded LBs were able to efficiently deliver siRNA or microRNA by systemic administration. A combination of LBs and diagnostic ultrasound also enhanced the imaging efficiency. Using a hindlimb ischemia mouse model, microRNA-loaded LBs could lead to increased angiogenic factors and improved blood flow. Conclusion: Ultrasound technology is widely used in clinical settings not only for diagnosis but also for therapy. Ultrasonic devices are being actively developed. Computer-controlled ultrasound systems can provide precise exposure to the target site. The combination of precise ultrasound exposure and LBs might be useful for target site-specific nucleic acids delivery, and holds potential to be developed into a beneficial therapeutic and diagnostic system for various diseases.

scholarly journals Solid-phase supported design of carriers for therapeutic nucleic acid delivery

2017 ◽  
Vol 37 (5) ◽  
Author(s):  
Ana Krhac Levacic ◽  
Stephan Morys ◽  
Ernst Wagner
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Solid Phase ◽  
Nucleic Acid Delivery ◽  
Chemical Production ◽  
Nucleic Acid Therapeutics ◽  
Gene Therapies ◽  
Current Review ◽  
Medical Translation ◽  
Site Of Action

Nucleic acid molecules are important therapeutic agents in the field of antisense oligonucleotide, RNA interference, and gene therapies. Since nucleic acids are not able to cross cell membranes and enter efficiently into cells on their own, the development of efficient, safe, and precise delivery systems is the crucial challenge for development of nucleic acid therapeutics. For the delivery of nucleic acids to their intracellular site of action, either the cytosol or the nucleus, several extracellular and intracellular barriers have to be overcome. Multifunctional carriers may handle the different special requirements of each barrier. The complexity of such macromolecules however poses a new hurdle in medical translation, which is the chemical production in reproducible and well-defined form. Solid-phase assisted synthesis (SPS) presents a solution for this challenge. The current review provides an overview on the design and SPS of precise sequence-defined synthetic carriers for nucleic acid cargos.

scholarly journals The Nanosystems Involved in Treating Lung Cancer

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 682
Author(s):  
Andreea Crintea ◽  
Alina Gabriela Dutu ◽  
Gabriel Samasca ◽  
Ioan Alexandru Florian ◽  
Iulia Lupan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Side Effects ◽  
Chromosomal Rearrangements ◽  
Sirna Delivery ◽  
Delivery Systems ◽  
Inorganic Nanoparticles ◽  
New Methods ◽  
Different Types ◽  
Or Gene ◽  
The Many

Even though there are various types of cancer, this pathology as a whole is considered the principal cause of death worldwide. Lung cancer is known as a heterogeneous condition, and it is apparent that genome modification presents a significant role in the occurrence of this disorder. There are conventional procedures that can be utilized against diverse cancer types, such as chemotherapy or radiotherapy, but they are hampered by the numerous side effects. Owing to the many adverse events observed in these therapies, it is imperative to continuously develop new and improved strategies for managing individuals with cancer. Nanomedicine plays an important role in establishing new methods for detecting chromosomal rearrangements and mutations for targeted chemotherapeutics or the local delivery of drugs via different types of nano-particle carriers to the lungs or other organs or areas of interest. Because of the complex signaling pathways involved in developing different types of cancer, the need to discover new methods for prevention and detection is crucial in producing gene delivery materials that exhibit the desired roles. Scientists have confirmed that nanotechnology-based procedures are more effective than conventional chemotherapy or radiotherapy, with minor side effects. Several nanoparticles, nanomaterials, and nanosystems have been studied, including liposomes, dendrimers, polymers, micelles, inorganic nanoparticles, such as gold nanoparticles or carbon nanotubes, and even siRNA delivery systems. The cytotoxicity of such nanosystems is a debatable concern, and nanotechnology-based delivery systems must be improved to increase the bioavailability, biocompatibility, and safety profiles, since these nanosystems boast a remarkable potential in many biomedical applications, including anti-tumor activity or gene therapy. In this review, the nanosystems involved in treating lung cancer and its associated challenges are discussed.

Reduction-Responsive Nucleic Acid Delivery Systems To Prevent In-Stent Restenosis in Rabbits

2019 ◽  
Vol 11 (31) ◽  
pp. 28307-28316 ◽  
Author(s):  
Weijie Ye ◽  
Yiming Chen ◽  
Wenxiong Tang ◽  
Na Zhang ◽  
Zhonghao Li ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Delivery Systems ◽  
Nucleic Acid Delivery ◽  
Stent Restenosis ◽  
In Stent Restenosis

scholarly journals The Impact of Alkyl‐Chain Purity on Lipid‐Based Nucleic Acid Delivery Systems – Is the Utilization of Lipid Components with Technical Grade Justified?

ChemPhysChem ◽  
2019 ◽  
Vol 20 (16) ◽  
pp. 2110-2121
Author(s):  
Dorota Pawlowska ◽  
Christopher Janich ◽  
Andreas Langner ◽  
Bodo Dobner ◽  
Christian Wölk ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Alkyl Chain ◽  
Delivery Systems ◽  
Nucleic Acid Delivery ◽  
Technical Grade ◽  
The Impact ◽  
Lipid Components

scholarly journals In Situ Loading and Delivery of Short Single- and Double-Stranded DNA by Supramolecular Organic Frameworks

CCS Chemistry ◽  
2019 ◽  
Vol 1 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Bo Yang ◽  
Xiao-Dan Zhang ◽  
Jian Li ◽  
Jia Tian ◽  
Yi-Peng Wu ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Dna Sequences ◽  
Laser Scanning ◽  
High Stability ◽  
Intracellular Delivery ◽  
Water Soluble ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Nucleic Acid Delivery

Short DNA represents an important class of biomacromolecules that are widely applied in gene therapy, editing, and modulation. However, the development of simple and reliable methods for their intracellular delivery remains a challenge. Herein, we describe that seven water-soluble, homogeneous supramolecular organic frameworks (SOFs) with a well-defined pore size and high stability in water that can accomplish in situ inclusion of single-stranded (ss) and double-stranded (ds) DNA (21, 23, and 58 nt) and effective intracellular delivery (including two noncancerous and six cancerous cell lines). Fluorescence quenching experiments for single and double end-labeled ss- and ds-DNA support that the DNA sequences can be completely enveloped by the SOFs. Confocal laser scanning microscopy and flow cytometry reveal that five of the SOFs exhibit excellent delivery efficiencies that, in most of the studied cases, outperform the commercial standard Lipo2000, even at low SOF–nucleic acid ratios. In addition to high delivery efficiencies, the water-soluble, self-assembled SOF carriers have a variety of advantages, including convenient preparation, high stability, and in situ DNA inclusion, which are all critical for practical applications in nucleic acid delivery.

Sign in / Sign up

Export Citation Format

Share Document