Bioconjugate Chemistry2020ReviewNon-viral Gene Delivery
Francia V, Schiffelers Rm, Cullis Pr, Witzigmann D
LNPs are clinically advanced vectors for siRNA, mRNA, and DNA delivery, but their in vivo behaviour is strongly influenced by the biological environment. Upon administration, biomolecules adsorb to the LNP surface and form a “biomolecular corona,” which defines the particle’s biological identity, affects stability…
Read the article →Advanced Drug Delivery Reviews2020ReviewDrug Delivery
Nina Filipczak, Jiayi Pan, Satya Siva Kishan Yalamarty, Vladimir P. Torchilin
Liposomes remain an important nano-sized drug delivery system because of their biomimetic bilayer, ease of preparation, and biocompatibility, but clinical translation is still limited by reproducibility, scale-up, stability, and payload-specific barriers. The review updates recent advances in liposome preparation…
Read the article →Expert Opinion on Drug Delivery2020ReviewNon-viral Gene Delivery
Karlsson, J.; Rhodes, K. R.; Green, J. J.; Tzeng, S. Y
Non-viral gene delivery needs safe and efficient carriers. PBAEs are biodegradable cationic polymers with promising transfection activity, but they face challenges such as instability in physiological fluids, positive-charge toxicity, and limited systemic delivery. This review summarises PBAE properties, advantages…
Read the article →Pharmaceutics2020ReviewNon-viral Gene Delivery
Wahane A, Waghmode A, Kapphahn A, Dhur K, Gupta A, Bahal R
Nucleic acid analogs and genome-editing proteins have broad therapeutic potential, but clinical translation is limited by poor cell- and organ-specific delivery, endosomal entrapment, enzymatic degradation, and short bioavailability. The review examines lipid- and polymer-based non-viral vectors as strategies to…
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…
Read the article →Nano Letters2019ResearchNon-viral Gene Delivery
Yuhang Jiang, Qiao Lu, Yongheng Wang, Emily Xu, Alison Ho, Priya Singh, Yifei Wang, Zhaozhong Jiang, Fan Yang, Gregory T. Tietjen, Peter Cresswell, W. Mark Saltzman
Endosomal escape is a key but poorly quantified step for intracellular nucleic acid delivery. Existing methods are low-throughput, indirect, or fail to distinguish endosomal disruption from actual cytosolic cargo delivery. A reliable, sensitive method is needed to rationally optimise polymeric mRNA delivery vehicles…
Read the article →Cancer Letters2019ReviewNon-viral Gene Delivery
Mukalel Aj, Riley Rs, Zhang R, Mitchell Mj.
Nucleic acid therapeutics—DNA, mRNA, and CRISPR/Cas9 genome editing systems—hold significant potential for cancer immunotherapy but face major delivery barriers, including rapid in vivo degradation, poor cellular uptake, required nuclear entry, and toxicity in healthy tissues. Nanoparticle delivery systems are being…
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…
Read the article →Journal of Pharmaceutical Investigation2019ReviewDrug Delivery
PLA and PLGA are FDA-approved, biodegradable polymers widely used for micro- and nanoparticle drug delivery, but their clinical performance depends on biocompatibility, degradation behaviour, and drug-release control. This review addresses the need to understand PLA/PLGA tissue responses, degradation pathways…
Read the article →Therapeutic Delivery* (Future Science Group) Year/Publication: Published online 4 December 20182018ReviewNon-viral Gene Delivery
Not Fully Listed In The Supplied File; Corresponding Authors Indicated By Emails: [email protected] And [email protected] Doi/link: Not Included In The Supplied File
Endosomal escape remains a major roadblock for delivering biological therapeutics such as DNA, siRNA, and proteins. Polymeric nanoparticles can protect cargo and target cells, but they often remain trapped in endosomal/lysosomal compartments, where cargo is degraded. A better understanding of how nanoparticle…
Read the article →Proceedings of the National Academy of Sciences (PNAS)2018ResearchNon-viral Gene Delivery
Ole A. W. Haabeth, Timothy R. Blake, Colin J. Mckinlay, Robert M. Waymouth, Paul A. Wender, Ronald Levy
mRNA-based cancer vaccination is a promising approach for personalised immunotherapy, but safe and effective mRNA delivery remains a major challenge due to mRNA's instability and poor cell membrane permeability. While lipid nanoparticles (LNPs) are the primary delivery strategy, they have limitations with respect to…
Read the article →PNAS2018ResearchNon-viral Gene Delivery
Colin J. Mckinlay, Nancy L. Benner, Ole A. Haabeth, Robert M. Waymouth, Paul A. Wender
Efficient mRNA delivery to lymphocytes remains a major unmet need for immunotherapy and vaccinology. Current methods rely largely on physical transfection such as electroporation, which is ex vivo, costly, and inefficient; chemical vectors generally achieve low lymphocyte mRNA transfection, especially in vivo. Lead…
Read the article →Journal of Controlled Release2018ResearchNon-viral Gene Delivery
Brynn R. Olden, Yilong Cheng, Jonathan L. Yu, Suzie H. Pun
CAR T cell immunotherapy requires efficient ex vivo gene delivery to primary human T cells, but viral vectors have limitations including cost, cargo size, insertional mutagenesis risk, and manufacturing complexity. Non-viral cationic polymers are attractive alternatives but historically show low gene transfer…
Read the article →Advanced Healthcare Materials (Adv. Healthcare Mater.)2018ResearchNon-viral Gene Delivery
Sungjin Min, Yoonhee Jin, Chen Yuan Hou, Jayoung Kim, Jordan J. Green, Taek Jin Kang, Seung-Woo Cho
Current cancer treatments (chemotherapy, radiotherapy) suffer from a lack of selectivity for tumour cells, causing severe side effects and therapeutic resistance. While gene therapy is a promising alternative, viral vectors pose safety risks (immunogenicity, tumorigenicity), and nonviral vectors often suffer from low…
Read the article →Small Methods.2018ReviewNon-viral Gene Delivery
Evers Mjw, Kulkarni Ja, Van Der Meel R, Cullis Pr, Vader P, Schiffelers Rm
Free siRNA, mRNA, pDNA, and CRISPR/Cas9 components are rapidly degraded and cleared, so delivery systems are required. LNPs are the most clinically advanced non-viral siRNA carriers; Patisiran reached Phase III and market application in late 2017. The field needed a clearer understanding of LNP design parameters and…
Read the article →Nature Communications2017ResearchNon-viral Gene Delivery
H.F. Moffett, M.E. Coon, S. Radtke, S.B. Stephan, L. Mcknight, A. Lambert, B.L. Stoddard, H.P. Kiem, M.T. Stephan
Therapies based on genetically engineered immune cells (CAR T cells, HSCs) are transforming medicine, but the viral and electroporation methods used to create these cytoreagents are complex, expensive, and time-consuming. There is a growing need for transient "hit-and-run" genetic programming (transcription factors…
Read the article →2017ReviewNon-viral Gene Delivery
Jiménez Blanco Jl, Benito Jm, Ortiz Mellet C, García Fernández Jm.
Nonviral gene delivery lacks molecularly well-defined carriers suitable for rigorous structure–activity relationship (SAR) studies. Viral vectors raise immunogenicity, cost, and cargo-size concerns, while polymers, dendrimers, and cationic lipids are often polydisperse or supramolecularly ill-defined. The review…
Read the article →Nature Reviews Materials2017ReviewNon-viral Gene Delivery
Khalid A. Hajj And Kathryn A. Whitehead
mRNA therapeutics have enormous potential for vaccines, cancer immunotherapy, protein replacement, and gene editing, but widespread clinical application is limited by the lack of safe and effective delivery vehicles. Naked mRNA is large (~10⁵–10⁶ Da), densely negatively charged, and rapidly degraded by nucleases; its…
Read the article →Journal of Controlled Release.2017ReviewNon-viral Gene Delivery
Tapeinos C, Battaglini M, Ciofani G
Delivery of therapeutics to the CNS is severely limited by the blood–brain barrier (BBB). Polymeric and inorganic nanoparticles have shown utility but face toxicity, scalability, and organic-solvent concerns. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are biocompatible lipid-based…
Read the article →Molecular Therapy2017ReviewNon-viral Gene Delivery
Cullis Pr, Hope Mj
Genetic drugs such as siRNA, mRNA, and plasmid DNA could treat most diseases by silencing pathological genes, expressing therapeutic proteins, or enabling gene editing. However, naked RNA/DNA is rapidly degraded, does not accumulate in target tissues, and cannot cross cell membranes efficiently. Lipid nanoparticles…
Read the article →WIREs Nanomedicine and Nanobiotechnology2017ReviewNon-viral Gene Delivery
Selby, L. I.; Cortez-Jugo, C. M.; Such, G. K.; Johnston, A. P. R
Endosomal escape is widely considered the rate-limiting bottleneck for cytoplasmic delivery of nucleic acids, proteins, and other therapeutics using polymeric and lipid nanoparticles. The field lacks robust methods to quantify escape efficiency and understand its mechanisms, limiting rational design of improved…
Read the article →Advanced Drug Delivery Reviews2016ReviewNon-viral Gene Delivery
Jayoung Kim, Adam C. Mirando, Aleksander S. Popel, Jordan J. Green
Angiogenesis is normally balanced by pro- and anti-angiogenic factors, but imbalance leads to aberrant angiogenesis in ischaemia, tissue regeneration, cancer, and neovascular age-related macular degeneration (wet AMD). Gene therapy is a promising strategy to introduce exogenous nucleic acids that express or silence…
Read the article →Journal of Controlled Release2016ReviewNon-viral Gene Delivery
Kevin J. Kauffman, Matthew J. Webber, Daniel G. Anderson
mRNA therapeutics have broad potential for protein replacement therapy, cancer immunotherapy, and genomic engineering, but effective intracellular delivery remains a major challenge. A chemically diverse suite of delivery materials—originally developed for DNA and siRNA transfection—has recently shown promise for…
Read the article →Journal of Biomedical Nanotechnology2016ResearchNon-viral Gene Delivery
Stephen L. Hayward, David M. Francis, Parviz Kholmatov, Srivatsan Kidambi
miRNA-based therapeutics are limited by instability, poor cellular uptake, lack of targeting, and potential immune activation. No nonviral miRNA delivery strategy had been explored as a standalone treatment for HER2-positive metastatic breast cancer. HA-LNP uptake was significantly higher than naked FITC-dextran and…
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