Polymeric nucleic acid delivery for immunoengineering

Abstract

Nucleic acids hold promise as tools for engineering the immune system. However, for use in patients, their delivery must be improved to overcome challenges in specificity and intracellular delivery efficiency. Polymers, both natural and synthetic, are under investigation as nucleic acid delivery vehicles, and their chemical and physical properties are being engineered to enhance their efficacy. Through formulation with polymers, DNA, mRNA, siRNA, and other nucleic acids can serve as prophylactic or therapeutic vaccines by overexpressing or knocking down expression of genes that affect the immune response. Polymeric delivery is also useful for the transport of intrinsically immunostimulatory nucleic acids to specific compartments of cells. Recent innovative examples of polymer-based nucleic acid vaccines and immunomodulatory strategies will be discussed.

Polymer-Based Nanosystems—A Versatile Delivery Approach

“…In this respect, nucleic acids can be employed for overexpressing or knocking down specific genes and can be used as adjuvants or danger signals for modulating the behavior of immune cells. Nonetheless, the direct delivery of nucleic acids has several drawbacks, as naked nucleic acids are prone to extracellular degradation, and they face difficulties in passing through the cell membrane [19,271,272].…”

“…Moreover, certain polymers' innate antimicrobial, antitumor, or immunostimulant properties can amplify therapeutic outcomes of corresponding incorporated drugs and vaccines [13][14][15][16]. Thus, polymer-based nanoparticles can be employed in the prophylaxis and treatment of various infectious, chronic, or genetic diseases [17][18][19].…”

Gene delivery for immunoengineering

“…Sarah Y Neshat 1 , Stephany Y Tzeng 1 and Jordan J Green 1,2,3,4,5 A growing number of gene delivery strategies are being employed for immunoengineering in applications ranging from infectious disease prevention to cancer therapy. Viral vectors tend to have high gene transfer capability but may be hampered by complications related to their intrinsic immunogenicity.…”

“…Here, we will discuss the delivery of plasmid DNA (pDNA) and mRNA to overexpress a gene of interest; oligonucleotides such as small interfering RNA (siRNA) and micro RNA (miRNA), which can knock down gene expression; and immunostimulatory nucleic acids that elicit a specific immune response. Differences in their physical, chemical, and immunological properties have been discussed in detail elsewhere [2]. Briefly, pDNA, the largest of these and generally >2 kb in size, is double-stranded and relatively stable to chemical degradation, but it must enter the nucleus.…”

Polymeric micro- and nanoparticles for immune modulation

“…The review will not cover other important areas in drug delivery for immunomodulation such as gene delivery (to which the reader is directed to a comprehensive review on the topic). 17 Both activation of the immune system, such as against cancer cells or infectious diseases, and suppression of the immune system, such as in the case of autoimmune disorders and transplant tolerance, will be described. As each particulate system is designed based on the specific immune cell type that it modulates, this review is structured based on these cell types: antigen presenting cells (APCs) including dendritic cells and macrophages, T cells, B cells, and NK Cells.…”