Cationic lipids, phosphatidylethanolamine and the intracellular delivery of polymeric, nucleic acid-based drugs (Review)

Nucleic acid-based therapeutics such as siRNA and miRNA employ the silencing capabilities of the RNAi mechanism to affect the expression of one gene or several genes in target cells. Nucleic acid-based therapies enable accurate, targeted administration and overcoming drug resistance in diverse cancer cells. Several studies have shown that they can be utilized alongside pharmacological therapy to increase the efficacy of existing therapies. In addition, nucleic acid-based therapies have the potential to widen the spectrum of druggable targets for a range of diseases and emerge as a novel therapeutic technique for treating a number of diseases that are today untreatable. Nucleic acids are dependent on their effective distribution to target cells, which need correct complexation and encapsulation in a delivery mechanism. Although nucleic acids exist in a variety of forms and sizes, their physical and chemical commonality allow them to be loaded into a wide range of delivery vehicles. The primary biomaterials used to encapsulate genetic components were cationic lipids and polymers. Furthermore, the experiments focused particularly on effective transfection in target cells.Recent breakthroughs in NP-based RNA therapeutics have spurred a flood of clinical research, facing many challenges. In vivo, pharmacokinetics of different RNA-based medications must be researched to establish the viability and therapeutic potential of nucleic acid-based therapeutics. The U.S. Food and Drug Administration recently authorized many NP-based gene therapy. In 2019, Novartis authorized Zolgensma (onasemnogene abeparvovec-xioi) to treat spinal muscle atrophy. The first clinical research employing siRNA began in 2004 and is considered a milestone in nucleic acid-based drug development. Thirty clinical investigations have subsequently been completed. In 2018, the US FDA cleared Onpattro (Patisiran, Alnylam Pharmaceuticals) for the treatment of polyneuropathy caused by transthyretin amyloidosis.Several new generations of nucleic acid compositions employing polymer nanoparticles or liposomes are presently undergoing clinical testing. If allowed, the debut of nucleic acid-based treatments would represent a watershed event in immunotherapy. Advances in the design and development of biocompatible nanomaterials would allow us to overcome the above-mentioned problems and so show the potential to deliver nucleic acids in the treatment of a number of illnesses.

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Role of Lipid-Based and Polymer-Based Non-Viral Vectors in Nucleic Acid Delivery for Next-Generation Gene Therapy

Molecules ◽

10.3390/molecules25122866 ◽

2020 ◽

Vol 25 (12) ◽

pp. 2866 ◽

Cited By ~ 8

Author(s):

Aniket Wahane ◽

Akaash Waghmode ◽

Alexander Kapphahn ◽

Karishma Dhuri ◽

Anisha Gupta ◽

...

Keyword(s):

Gene Therapy ◽

Nucleic Acid ◽

Messenger Rna ◽

Viral Vectors ◽

Cationic Lipids ◽

Nucleic Acid Delivery ◽

Nucleic Acid Analogs ◽

Organ Specific ◽

Interfering Rna

The field of gene therapy has experienced an insurgence of attention for its widespread ability to regulate gene expression by targeting genomic DNA, messenger RNA, microRNA, and short-interfering RNA for treating malignant and non-malignant disorders. Numerous nucleic acid analogs have been developed to target coding or non-coding sequences of the human genome for gene regulation. However, broader clinical applications of nucleic acid analogs have been limited due to their poor cell or organ-specific delivery. To resolve these issues, non-viral vectors based on nanoparticles, liposomes, and polyplexes have been developed to date. This review is centered on non-viral vectors mainly comprising of cationic lipids and polymers for nucleic acid-based delivery for numerous gene therapy-based applications.

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Efficient cellular uptake of click nucleic acid modified proteins

Chemical Communications ◽

10.1039/c9cc09401f ◽

2020 ◽

Vol 56 (35) ◽

pp. 4820-4823 ◽

Cited By ~ 1

Author(s):

Albert Harguindey ◽

Heidi R. Culver ◽

Jasmine Sinha ◽

Christopher N. Bowman ◽

Jennifer N. Cha

Keyword(s):

Nucleic Acid ◽

Cellular Uptake ◽

Intracellular Delivery ◽

Modified Proteins

Efficient intracellular delivery of biomacromolecules such as proteins continues to remain a challenge despite its potential for medicine.

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

CCS Chemistry ◽

10.31635/ccschem.019.20180011 ◽

2019 ◽

Vol 1 (2) ◽

pp. 156-165 ◽

Cited By ~ 11

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.

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