DNA‐Based Biomaterials for Immunoengineering

Abstract

of extracellular DNA in tissues and in circulation. [5] Extracellular DNA is capable of engaging with the immune system as depicted in Figure 1; therefore, as synthetic DNA-based biomaterials emerge, their potential immune responses must be considered. DNA sensors are mediators of extracellular DNA immune responses observed in vivo, including cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) and toll-like receptors (TLRs). Defining novel DNA sensors and their mechanisms is an active area of investigation. [6] Likewise, the structural and chemical properties of DNA that triggers DNA sensors continue to be uncovered. [6] This review summarizes known DNA interaction modalities with the immune system, the sources of extracellular DNA, and, finally, the relevant and emerging biotechnologies that incorporate DNA molecules. A focus is geared toward innate immune responses and doublestranded DNA (dsDNA). Leveraging the immunomodulatory capacity of DNA enables tailoring materials to initiate specific immune outcomes depending on the application, for instance, priming aggressive immune responses for localized tumor-interfacing biomaterials or immunosuppressive functions to prevent chronic inflammation on implant surfaces. Achieving this requires an improved understanding of the DNA properties, such as backbone chemistry, base pair sequence, charge, and length, that can function as design levers for the immune response. The Role of Extracellular DNA in the Immune ResponseThe immune system is designed to protect the host against infections by distinguishing between self-and non-self motifs, and by identifying pathogen and damage signals. Upon recognition of a "non-self" or foreign molecule, an array of effector functions are triggered and orchestrated by immune cells to achieve pathogen clearance and restore homeostasis. [7] These immunoactivating defense mechanisms include the release of proinflammatory cytokines, immune cell recruitment, programmed cell death, and phagocytosis. Ideally, immunoactivating responses are supplanted by immunosuppressive functions once the pathogen or agonist is resolved. This immune resolution is necessary to coordinate healing and anti-inflammatory functions such as diminished chemokine and cytokine secretion, replacement Man-made DNA materials hold the potential to modulate specific immune pathways toward immunoactivating or immunosuppressive cascades. DNAbased biomaterials introduce DNA into the extracellular environment during implantation or delivery, and subsequently intracellularly upon phagocytosis or degradation of the material. Therefore, the immunogenic functionality of biological and synthetic extracellular DNA should be considered to achieve desired immune responses. In vivo, extracellular DNA from both endogenous and exogenous sources holds immunoactivating functions which can be traced back to the molecular features of DNA, such as sequence and length. Extracellular DNA is recognized as damage-associated molecular patterns (DAMPs), or pathogen-associated mole...

Nanomedicine‐Based Immunotherapy for the Treatment of Cancer Metastasis

“…[20][21][22][23][24][25] The convenience and efficacy of these treatments can be further improved with biomaterials and nanomedicines, [26][27][28][29][30][31][32][33] because they can deliver and release multiple biomacromolecules (such as antigens, antibodies, and nucleic acids) specifically to selected tissues and cells in spatial-, temporal-, and dosage-controlled fashions in response to exogenous or endogenous stimuli. [20][21][22][23][24][25] The convenience and efficacy of these treatments can be further improved with biomaterials and nanomedicines, [26][27][28][29][30][31][32][33] because they can deliver and release multiple biomacromolecules (such as antigens, antibodies, and nucleic acids) specifically to selected tissues and cells in spatial-, temporal-, and dosage-controlled fashions in response to exogenous or endogenous stimuli.…”

“…Currently, immune modulation therapies such as adoptive cell transfer (ACT), cytokines, and immune checkpoint blockers (ICBs) have been approved for cancer treatment, and many therapeutic vaccines are under clinical trials. [20][21][22][23][24][25] The convenience and efficacy of these treatments can be further improved with biomaterials and nanomedicines, [26][27][28][29][30][31][32][33] because they can deliver and release multiple biomacromolecules (such as antigens, antibodies, and nucleic acids) specifically to selected tissues and cells in spatial-, temporal-, and dosage-controlled fashions in response to exogenous or endogenous stimuli. [34,35] These treatments are effective against both primary and clinically detectable metastatic tumors in the targeted population, [36] but different fates of metastatic lesions are often observed posttherapy probably due to heterogeneous immune microenvironments among differentially growing metastasis.…”

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.…”

Biomaterials as Tools to Decode Immunity

“…In the immune field, biomaterials are used to deliver a range of vectors that either encode immune signals or bind complementary nucleic acid sequences involved in immune function; alternatively, the cargo are nucleic acid‐based ligands—such as TLR agonists—that trigger innate immune pathways, but do not directly encode genetic information (see Section ). Thus, precision delivery of DNA, messenger RNA (mRNA), microRNA (miR), small interfering RNA (siRNA), and other genetic molecules offer multiple levels to probe how the trafficking and processing of immune signals impacts immunity and regulation . The delivery of these different classes of nucleic acid will be discussed in this section.…”

“…Thus, precision delivery of DNA, messenger RNA (mRNA), microRNA (miR), small interfering RNA (siRNA), and other genetic molecules offer multiple levels to probe how the trafficking and processing of immune signals impacts immunity and regulation. [68][69][70][71][72] The delivery of these different classes of nucleic acid will be discussed in this section. Along these lines, innate immune cells have historically proven difficult to successfully transfect because of the efficiency with which these cells degrade nucleic acid and the limited proliferative capacity of these cells.…”