Rationally designed nanoparticle delivery of Cas9 ribonucleoprotein for effective gene editing

Development of a Cancer Nanovaccine to Induce Antigen-specific Immune Responses Based on Large-Sized Porous Silica Nanoparticles

“…We prepared PS3 according to our previous reports. , The physical properties of synthesized PS3 were analyzed using various methods. The PS3 was first characterized by transmission electron microscopy (TEM), which revealed an average diameter of 344 nm with a spherical shape (Figure A).…”

“…Nitrogen adsorption and desorption tests showed that the pore size of PS3 was 12.1 nm and the Brunauer–Emmett–Teller (BET) surface area was 351.2 m 2 /g (Figure S1A,B). To effectively deliver OVA, the pore size of PS3 should be large enough to encapsulate OVA (dimension: 7.0 × 3.6 × 3.0 nm) into the pore; however, very large pores could result in the burst release of cargo . Therefore, we synthesized a PS3 having an average pore size of 12.1 nm.…”

“…To effectively deliver OVA, the pore size of PS3 should be large enough to encapsulate OVA (dimension: 7.0 × 3.6 × 3.0 nm) into the pore; however, very large pores could result in the burst release of cargo. 24 Therefore, we synthesized a PS3 having an average pore size of 12.1 nm. Due to the positively charged surface of PS3, OVA, which is a negatively charged model antigen (pI: 4.54), could be loaded to PS3 via electrostatic interaction at neutral pH.…”

Confinement in Dual-Chain-Locked DNA Origami Nanocages Programs Marker-Responsive Delivery of CRISPR/Cas9 Ribonucleoproteins

“…Only in the presence of ATP was the gene cleavage activity of AL-DONCs-Cas9 switched on and thus generated more cleaved substrates, as compared to AL-DONCs-Cas9 without ATP activation and Cas9 RNPs-loaded DONCs without chain locks (UL-DONCs-Cas9) (Figure S13a). In a more complex biological system (2% fetal bovine serum, FBS), DONCs showed a great protective effect for maintaining the cleavage efficiency of Cas9 RNPs, whereas the free Cas9 RNPs appeared to be deactivated (Figure S13b), which may be attributed to the probable degradation of RNPs by proteases or endo/exonucleases in serum. , Even in 90% FBS, AL-DONCs-Cas9 exhibited a sustained cleavage activity for a duration of 10 h, whereas free Cas9 RNPs completely lost their cleavage capability after 6 h (Figure S14). These compelling comparisons emphasized the promising potential of chain-locked DONCs for overcoming the complexity of biological environments during Cas9 RNP delivery.…”

Enhanced Local Delivery of Engineered IL-2 mRNA by Porous Silica Nanoparticles to Promote Effective Antitumor Immunity

“…Porous silica nanoparticles (PSNs) have emerged as promising drug delivery vehicles due to their tunable physicochemical properties, such as particle size, pore size, pore structure, and surface functionality. ,, In our previous studies, we demonstrated the highly efficient delivery of siRNA and Cas9 ribonucleoprotein (RNP) using PSNs, with a sustained release profile. Recently, we have investigated the use of PSNs for antigen delivery and demonstrated the ability to induce a scaffold structure at the injection site, as well as sustained release of antigen upon subcutaneous injection .…”