Angewandte Chemie International Edition2020ReviewNon-viral Gene Delivery
Shuangqian Yan, Zichao Luo, Zhenglin Li, Yu Wang, Jun Tao, Changyang Gong, Xiaogang Liu
Cancer immunotherapy has improved clinical outcomes, but few patients show adequate response rates and long-term responses, and systemic side effects remain common due to the dynamic nature of the immune system. Biomaterial-assisted immunotherapy is a promising approach to improve therapeutic efficacy and reduce side effects. --- - DNA–RNA nanocapsules: augmented neoantigen-specific peripheral CD8+ T cell responses more than 8-fold relative to CpG controls and prevented growth of neoantigen-specific colorectal tumors. - Nanovaccine: OVA/ICG nanovaccines showed high antigen-loading efficiency of 80.8% and enabled imaging-guided photothermal immunotherapy. - STING nanoparticles: pH-responsive polymer nanoparticles delivering cGAMP potently inhibited B16F10 growth by stimulating an immunogenic, T-cell-inflamed tumor microenvironment. - Liposome platform HMME/R837@Lip: combined with checkpoint blockade inhibited tumor growth and metastases
Read the article →Acta Biomaterialia (Published by Elsevier Ltd on behalf of Acta Materialia Inc.)2020ResearchNon-viral Gene Delivery
Kelly R. Rhodes, Randall A. Meyer, Justin Wang, Stephany Y. Tzeng, Jordan J. Green
Regulatory T cell (Treg)-based therapeutics show promise for treating autoimmune diseases and preventing transplant rejection, but adoptive Treg transfer is expensive, complex, and difficult to implement. "Off-the-shelf" non-cellular alternatives that can induce endogenous Tregs in vivo are needed. Existing artificial antigen presenting cells (aAPCs) are typically used for ex vivo T cell expansion and have limited application for immune. ### Protein Conjugation & aAPC Characterization | Parameter | PLGA aAPC | PLGA/PBAE aAPC | Significance | |---------------|---------------|--------------------|------------------| | Anti-CD3 conjugation (1× dose) |.
Read the article →Molecular Therapy2019ReviewNon-viral Gene Delivery
Piotr S. Kowalski, Arnab Rudra, Lei Miao, Daniel G. Anderson
mRNA has broad therapeutic potential for vaccination, protein replacement, and gene editing, but its clinical translation is limited by the need for improved intracellular delivery systems. mRNA is much larger than siRNA or ASOs (~300–5,000 kDa, ~1–15 kb vs ~14 kDa and 4–10 kDa, respectively), making delivery more challenging. This review addresses the gap between mRNA's therapeutic promise and the delivery barriers that still restrict its broad application. --- - Protein expression half-life: Modified mRNA protein production half-life ranges from ~50 h in vitro to 7–30 h in vivo, depending on route. Circular RNAs provide up to 3-fold increase in half-life in vitro. - Liver expression: LNPs with lipid 5 achieved hEPO expression at doses as low as 0.01 mg/kg in NHPs, with peak expression at 6–12 h and sustained for over a month with weekly dosing. - Gene editing: LNP-mediated co-delivery of Cas9 mRNA and sgRNA achieved >80% indels for PC
Read the article →Nature Reviews Drug Discovery.2019ReviewNon-viral Gene Delivery
Rachel S. Riley, Carl H. June, Robert Langer, Michael J. Mitchell.
Immunotherapy has become powerful but broad implementation limited by inability to control immune modulation; serious adverse effects including autoimmunity, nonspecific inflammation. Need delivery technologies to improve efficacy and safety. Numbers.
Read the article →Biomaterials2019ReviewNon-viral Gene Delivery
Zhao W, Hou X, Vick Og, Dong Y.
Genetic and rare diseases (GARDs) affect more than 350 million patients worldwide, and many lack effective treatments. RNA-based therapeutics—siRNA, mRNA, miRNA, lncRNA, and RNA-containing genome editing systems—are promising, but naked RNA has poor cellular penetration, is degraded in biological fluids, and does not accumulate in target organs after systemic administration. Non-viral RNA delivery biomaterials are needed to enable systemic. Patisiran became the first FDA-approved siRNA drug in 2018; LNP delivers siRNA to hepatocytes, targeting TTR for hATTR. - DLin-KC2-DMA SNALPs showed in vivo activity at 0.01 mg/kg in mice and TTR silencing ED50 ~0.3.
Read the article →2019ReviewNon-viral Gene Delivery
Gheibi Hayat Sm, Bianconi V, Pirro M, Sahebkar A.
Biomaterials and nanoparticles (NPs) used for medical purposes often trigger immune recognition, inflammation, and rapid clearance by the reticuloendothelial system (RES)/mononuclear phagocyte system (MPS). PEGylation and cell-membrane camouflaging are common stealth strategies, but they have limitations, including anti-PEG immune responses. CD47, a “don’t-eat-me” signal, is emerging as an alternative stealth functionalization to improve. CD47-coated polystyrene beads reduced macrophage phagocytosis by 50% compared with CD47-free beads; anti-CD47 antibody abolished the effect. - CD47 immobilization on PVC tubing almost completely inhibited cell.
Read the article →Materials2017ReviewNon-viral Gene Delivery
Sun, X.; Wu, G.; Xu, C.; Ye, Q.; Wang, C
Periodontitis causes irreversible destruction of periodontal tissues, and regeneration requires biomaterials with suitable mechanical, degradation, and biological properties. PLGA is attractive for periodontal regeneration because of its biocompatibility, tunable degradation, and processability, but its hydrophobicity and limited bioactivity restrict performance. This review summarizes PLGA properties and progress as barrier membranes, bone. Rhesus monkey intrabony defects: PLGA membrane vs flap only: new cementum 2.74 vs 0.20 mm, new bone 2.64 vs 0.19 mm, connective tissue adhesion 2.80 vs 0.20 mm. - Class II furcation defects: PLGA membranes gave 250–350%.
Read the article →Nature2016ReviewNon-viral Gene Delivery
Green, J. J.; Elisseeff, J. H
Biomaterials must increasingly do more than simply avoid rejection; they must actively mimic biological structures and functions to direct cell behavior, modulate immunity, and repair tissues. This review addresses how biologically inspired polymers can be designed for local tissue engineering, systemic therapeutic functions, and interfacial applications such as adhesives and lubricious coatings. Worm-like polymeric DNA nanoparticles delivered genes to rat liver with expression two and three orders of magnitude higher than rod-like nanoparticles and nanospheres, respectively. - Ellipsoidal aAPCs with high aspect.
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