A High‐Throughput Platform for Formulating and Screening Multifunctional Nanoparticles Capable of Simultaneous Delivery of Genes and Transcription Factors

Abstract

Simultaneous delivery of multiple genes and proteins (e.g., transcription factors; TFs) is an emerging issue surrounding therapeutic research due to their ability to regulate cellular circuitry. Current gene and protein delivery strategies, however, are based on slow batch synthesis, which is ineffective, poorly controlled, and incapable of simultaneous delivery of both genes and proteins with synergistic functions. Consequently, advances in this field have been limited to in vitro studies. Here, by integrating microfluidic technologies with a supramolecular synthetic strategy, we present a high‐throughput approach for formulating and screening multifunctional supramolecular nanoparticles (MFSNPs) self‐assembled from a collection of functional modules to achieve simultaneous delivery of one gene and TF with unprecedented efficiency both in vitro and in vivo. We envision that this new approach could open a new avenue for immunotherapy, stem cell reprogramming, and other therapeutic applications.

Efficient Gene Delivery Mediated by a Helical Polypeptide: Controlling the Membrane Activity via Multivalency and Light-Assisted Photochemical Internalization (PCI)

“…17−20 A major obstacle against polycation-mediated gene delivery is the biological membranes, such as cell membranes, endosomal/lysosomal membranes, and nuclear membranes. 17,21 As such, the development of membrane-penetrating materials represents a promising approach for nonviral gene delivery.…”

Exploiting recent trends for the synthesis and surface functionalization of mesoporous silica nanoparticles towards biomedical applications

“…Small interference RNA (siRNA) has shown great promise in gene therapy because it can efficiently silence the expression of the desired target with high specificity and minimal side effects. Despite the great promise of siRNA in biomedical application, there have been several obstacles that restrict their clinical application, which includes: (i) naked siRNA is easily degradable by endogenous nucleases with rapid clearance by the renal route and (ii) they cannot be internalized efficiently by target cells due to polar nature of phospholipid bilayer membrane ( Chen et al, 2015 ; de Fougerolles et al, 2007 ; Liu et al, 2016 ; van den Brand et al, 2018 ). Nowadays, enormous efforts have been devoted to developing nanoparticles for gene therapeutics.…”

Supramolecular nanosubstrate–mediated delivery system enables CRISPR-Cas9 knockin of hemoglobin beta gene for hemoglobinopathies

“…Our previous experience in using SMNP vectors for coencapsulating a transcription factor protein and a DNA plasmid (26) was used to prepare Cas9•sgRNA⊂SMNPs (Fig. 1B).…”