Polyethylenimine (PEI) in gene therapy: Current status and clinical applications

Recent Advances in Stimuli-Responsive Self-Immolative Polymers for Drug Delivery and Molecular Imaging

“…113,114 Cationic polymers, such as polyethylenimine (PEI) and polyamidoamine (PAMAM), are generally nonimmunogenic and conveniently scalable for production, making them widely applicable in gene transfection. 115,116 However, their clinical application is limited due to their high cytotoxicity, nondegradability, and difficulty in rapid nucleic acid release.…”

“…Additionally, mRNA vaccines have played a significant role in the prevention and treatment of COVID-19 . One of the challenges in gene therapy is the lack of efficient carriers that can deliver nucleic acids to specific regions of target cells and release DNA/RNA rapidly. , Cationic polymers, such as polyethylenimine (PEI) and polyamidoamine (PAMAM), are generally nonimmunogenic and conveniently scalable for production, making them widely applicable in gene transfection. , However, their clinical application is limited due to their high cytotoxicity, nondegradability, and difficulty in rapid nucleic acid release.…”

Degradable Cationic Polycarbamates Designed for Robust IL-12 Gene Therapy against Metastatic Lung Cancer

“…2 In this regard, 25 kDa branched PEI (BPEI) is well recognized as one of the most potent polymeric carriers for in vitro gene delivery against different cancer cells because of its robust gene binding ability to form nanopolyplexes and high buffering capacity to help efficient gene escape from acidified endosomes. 3 However, the BPEI was not frequently applied for in vivo gene delivery due to its awfully high cytotoxicity and the lack of high transgene expression in targeted tissues. 4 To address these issues, various chemical modifications of the BPEI, such as traditional PEGylation, were studied extensively for targeted gene delivery.…”

“…Among these carriers, the polyethylenimines (PEIs) containing several protonatable amino groups have received much attention on their applications for nonviral gene therapy against cancers . In this regard, 25 kDa branched PEI (BPEI) is well recognized as one of the most potent polymeric carriers for in vitro gene delivery against different cancer cells because of its robust gene binding ability to form nanopolyplexes and high buffering capacity to help efficient gene escape from acidified endosomes . However, the BPEI was not frequently applied for in vivo gene delivery due to its awfully high cytotoxicity and the lack of high transgene expression in targeted tissues .…”

Assembly of ionic supramolecular polymers using a decacationic pillar[5]arene to noncovalently crosslink hyaluronic acid for short DNA delivery

“…34 We conjectured that positively charged supramolecular polymers might be formed using this strategy by endowing the pillararene units with a high density of positive charges. The resulting ionic supramolecular polymers might display nano-scale sizes and dynamic porous networks for loading bioactive guests, particularly short DNA, since all carriers of short DNA reported yet are polycationic 35–37 and porous supramolecular frameworks have been demonstrated as carriers that can more efficiently make use of multivalent ionic electrostatic interactions to load and deliver short DNA. 38,39 Short DNA or RNA molecules have found clinical applications, but suffer from the challenges of economical and efficient intramolecular delivery.…”