Challenges and Opportunities in Developing Therapeutic Nucleic Acid Cargo and Delivery

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: closed (25 May 2023) | Viewed by 7548

Special Issue Editors

Laboratory of Molecular Biology and Nanomedicine, Department of Orthopaedics, Brown University/Rhode Island Hospital, 1 Hoppin Street, Suite 402A, Providence, RI 02903, USA
Interests: nanomedicine; nucleic acid therapeutics; RNA; gene therapy; inflammation; bone and joint; cartilage; degenerative diseases; aging
Special Issues, Collections and Topics in MDPI journals
Laboratory of Molecular Biology and Nanomedicine, Department of Orthopaedics, Brown University/Rhode Island Hospital, 1 Hoppin Street, Suite 402A, Providence, RI 02903, USA
Interests: chemical engineering; organic synthesis; polymers; hydrogel; molecular modeling; tissue engineering
Department of Biological Systems Engineering, Institute of Agriculture and Natural Resources, College of Engineering, University of Nebraska–Lincoln, 368 Morrison Life Science Center, Lincoln, NE 68583-0900, USA
Interests: bioengineering; chemical priming; nonviral gene delivery; stem cells

Special Issue Information

Dear Colleagues,

Nucleic acid therapeutics is an emerging and exciting research field. Nothing illustrates its power better than mRNA vaccines against coronavirus, which have saved countless lives during the COVID-19 pandemic. The rapid development and production of mRNA vaccines is based on research in the nucleic acid therapeutics research field for many years prior to its success. More research and data are needed to sustain and expand the success of nucleic acid therapeutics. The main purpose of this Special Issue is to encourage the submission and publication of rigorous research and important findings in the nucleic acid therapeutic area. Recent advances in the field are based on cutting-edge molecular research, including gene therapy, gene silencing, and gene editing. Furthermore, chemical, physical, and biological modification of the nucleic acid cargo may improve stability, weaken immunogenicity, and reduce toxicity. Tissue and cellular delivery of nucleic acid therapeutics is the key since nucleic acid mainly functions within the cell, some of which within the nucleus.  Our body presents many barriers to drug delivery, such as dense connective tissues, solid tumors with high interstitial fluid pressure, and the blood–brain barrier. A technology to overcome the delivery challenges of nucleic acid therapeutics is essential. Finally, targeted delivery and sustained release of nucleic acid therapeutics will not only improve drug efficacy but also achieve precision medicine.

The journal Pharmaceuticals invites both reviews and original articles shedding light on the challenges and opportunities of developing nucleic acid therapeutics, including both cargo and delivery. Related disciplines including cell and molecular biology, pharmacology and pharmaceutics, chemical and bioengineering, and translational and clinical sciences are welcome. Topics include but are not restricted to DNA and RNA drugs; gene therapy; gene editing; messenger RNA and noncoding RNA; RNAi, including microRNA and siRNA; long noncoding RNA and circular RNA; oligonucleotides, including anti-sense oligos (ASO), chemical, physical, and biological modification of nucleic acid cargo; delivery vehicles, including virus (AAV), lipid nanoparticles (LNP), polymers, proteins and peptides, and small molecules; delivery routes, including local and systemic; technologies to improve targeting, drug release, and modulation of gene expression; CMC and drug synthesis and formulation; novel disease applications; and potential side effects.  The collection of manuscripts will be published as a Special Issue of the journal.

Prof. Dr. Qian Chen
Dr. Zhen Qiao
Dr. Andrew Hamann
Guest Editors

Manuscript Submission Information

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Keywords

  • nucleic acid therapeutics
  • gene therapy
  • gene editing
  • DNA
  • mRNA vaccine
  • RNAi
  • AAV
  • nonviral gene delivery
  • ASO
  • nucleic acid synthesis and delivery

Published Papers (3 papers)

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Research

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15 pages, 1771 KiB  
Article
mRNA-Loaded Lipid Nanoparticles Targeting Immune Cells in the Spleen for Use as Cancer Vaccines
Pharmaceuticals 2022, 15(8), 1017; https://doi.org/10.3390/ph15081017 - 18 Aug 2022
Cited by 10 | Viewed by 3460
Abstract
mRNA delivery has recently gained substantial interest for possible use in vaccines. Recently approved mRNA vaccines are administered intramuscularly where they transfect antigen-presenting cells (APCs) near the site of administration, resulting in an immune response. The spleen contains high numbers of APCs, which [...] Read more.
mRNA delivery has recently gained substantial interest for possible use in vaccines. Recently approved mRNA vaccines are administered intramuscularly where they transfect antigen-presenting cells (APCs) near the site of administration, resulting in an immune response. The spleen contains high numbers of APCs, which are located near B and T lymphocytes. Therefore, transfecting APCs in the spleen would be expected to produce a more efficient immune response, but this is a challenging task due to the different biological barriers. Success requires the development of an efficient system that can transfect different immune cells in the spleen. In this study, we report on the development of mRNA-loaded lipid nanoparticles (LNPs) targeting immune cells in the spleen with the goal of eliciting an efficient immune response against the antigen encoded in the mRNA. The developed system is composed of mRNA loaded in LNPs whose lipid composition was optimized for maximum transfection into spleen cells. Dendritic cells, macrophages and B cells in the spleen were efficiently transfected. The optimized LNPs produced efficient dose-dependent cytotoxic T lymphocyte activities that were significantly higher than that produced after local administration. The optimized LNPs encapsulating tumor-antigen encoding mRNA showed both prophylactic and therapeutic antitumor effects in mice. Full article
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15 pages, 2928 KiB  
Article
Reversing Cardiac Hypertrophy at the Source Using a Cardiac Targeting Peptide Linked to miRNA106a: Targeting Genes That Cause Cardiac Hypertrophy
Pharmaceuticals 2022, 15(7), 871; https://doi.org/10.3390/ph15070871 - 15 Jul 2022
Cited by 5 | Viewed by 1649
Abstract
Causes and treatments for heart failure (HF) have been investigated for over a century culminating in data that have led to numerous pharmacological and surgical therapies. Unfortunately, to date, even with the most current treatments, HF remains a progressive disease with no therapies [...] Read more.
Causes and treatments for heart failure (HF) have been investigated for over a century culminating in data that have led to numerous pharmacological and surgical therapies. Unfortunately, to date, even with the most current treatments, HF remains a progressive disease with no therapies targeting the cardiomyocytes directly. Technological advances within the past two to three years have brought about new paradigms for treating many diseases that previously had been extremely difficult to resolve. One of these new paradigms has been a shift from pharmacological agents to antisense technology (e.g., microRNAs) to target the molecular underpinnings of pathological processes leading to disease onset. Although this paradigm shift may have been postulated over a decade ago, only within the past few years has it become feasible. Here, we show that miRNA106a targets genes that, when misregulated, have been shown to cause hypertrophy and eventual HF. The addition of miRNA106a suppresses misexpressed HF genes and reverses hypertrophy. Most importantly, using a cardiac targeting peptide reversibly linked to miRNA106a, we show delivery is specific to cardiomyocytes. Full article
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Review

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13 pages, 679 KiB  
Review
Smart Strategies to Overcome Drug Delivery Challenges in the Musculoskeletal System
Pharmaceuticals 2023, 16(7), 967; https://doi.org/10.3390/ph16070967 - 06 Jul 2023
Viewed by 1404
Abstract
The musculoskeletal system (MSKS) is composed of specialized connective tissues including bone, muscle, cartilage, tendon, ligament, and their subtypes. The primary function of the MSKS is to provide protection, structure, mobility, and mechanical properties to the body. In the process of fulfilling these [...] Read more.
The musculoskeletal system (MSKS) is composed of specialized connective tissues including bone, muscle, cartilage, tendon, ligament, and their subtypes. The primary function of the MSKS is to provide protection, structure, mobility, and mechanical properties to the body. In the process of fulfilling these functions, the MSKS is subject to wear and tear during aging and after injury and requires subsequent repair. MSKS diseases are a growing burden due to the increasing population age. The World Health Organization estimates that 1.71 billon people suffer from MSKS diseases worldwide. MSKS diseases usually involve various dysfunctions in bones, muscles, and joints, which often result in pain, disability, and a decrease in quality of life. The most common MSKS diseases are osteoporosis (loss of bone), osteoarthritis (loss of cartilage), and sarcopenia (loss of skeletal muscle). Because of the disease burden and the need for treatment, regenerative drug therapies for MSKS disorders are increasingly in demand. However, the difficulty of effective drug delivery in the MSKS has become a bottleneck for developing MSKS therapeutics. The abundance of extracellular matrix and its small pore size in the MSKS present a formidable barrier to drug delivery. Differences of vascularity among various MSKS tissues pose complications for drug delivery. Novel strategies are necessary to achieve successful drug delivery in different tissues composing the MSKS. Those considerations include the route of administration, mechanics of surrounding fluids, and biomolecular interactions, such as the size and charge of the particles and targeting motifs. This review focuses on recent advances in challenges to deliver drugs to each tissue of the MSKS, current strategies of drug delivery, and future ideas of how to overcome drug delivery challenges in the MSKS. Full article
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