Insight Into the Molecular Parameters of PEI Promoting an Efficient Gene Delivery into Cells DOI Open Access
Paulina González, Sylvain Tranchimand,

Manon Rochedy

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 3, 2024

Abstract The development of natural or synthetic polycations able to interact with nucleic acids and condense them into nanoparticles known as polyplexes, faces several unresolved challenges at the cellular level. Key issues include intracellular trafficking endosomal escape release cytosol, which are considered major bottlenecks for efficient protein expression. Here, we aim gaining fundamental insights stability polyplexes in biological media their uptake trafficking, while correlating data expression reporter both molecular characteristics various poly(ethylenimines) (PEI) physicochemical PEI/peGFP-C3 polyplexes. For this, chosen four samples PEI, selected a model polycation, different weights (Mw = 0.8, 20, 25 60 kg/mol) structures (linear branched). We found that vitro vivo cell internalization transfection efficiency is dependent on variation polycation Mw structure, well intrinsic properties such charge ratio (R=[N + ]/[P − ]). A relation between percentage positive cells green fluorescent (GFP) amount internalized acid (cyanine 5-peGFP-C3) allowed revealing PEI promoting higher GFP HEK293T cells. In long term, outcome this work will be propose guidelines help design more effective, less cytotoxic non-viral gene carriers great potential new therapeutic applications.

Language: Английский

Recent Advances and Prospects of Nucleic Acid Therapeutics for Anti-Cancer Therapy DOI Creative Commons
Minhyuk Lee,

Min-Jae Lee,

Youngseo Song

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(19), P. 4737 - 4737

Published: Oct. 7, 2024

Nucleic acid therapeutics are promising alternatives to conventional anti-cancer therapy, such as chemotherapy and radiation therapy. While therapies have limitations, high side effects, low specificity, drug resistance, nucleic work at the gene level eliminate cause of disease. treat diseases in various forms using different mechanisms, including plasmid DNA (pDNA), small interfering RNA (siRNA), anti-microRNA (anti-miR), microRNA mimics (miRNA mimic), messenger (mRNA), aptamer, catalytic (CNA), CRISPR cas9 guide (gRNA). In addition, acids many advantages nanomaterials, biocompatibility, design flexibility, immunogenicity, size, relatively price, easy functionalization. can a therapeutic effect by being used combination with nanostructures, inorganic nanoparticles, lipid nanoparticles (LNPs), etc. overcome physiological stability cell internalization efficiency. The field has advanced remarkably recent decades, more been approved, they already demonstrated their potential diseases, cancer. This review paper introduces current status advances therapy for treatment discusses tasks prospects ahead.

Language: Английский

Citations

4
Insight Into the Molecular Parameters of PEI Promoting an Efficient Gene Delivery into Cells DOI Open Access
Paulina González, Sylvain Tranchimand,

Manon Rochedy

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 3, 2024

Abstract The development of natural or synthetic polycations able to interact with nucleic acids and condense them into nanoparticles known as polyplexes, faces several unresolved challenges at the cellular level. Key issues include intracellular trafficking endosomal escape release cytosol, which are considered major bottlenecks for efficient protein expression. Here, we aim gaining fundamental insights stability polyplexes in biological media their uptake trafficking, while correlating data expression reporter both molecular characteristics various poly(ethylenimines) (PEI) physicochemical PEI/peGFP-C3 polyplexes. For this, chosen four samples PEI, selected a model polycation, different weights (Mw = 0.8, 20, 25 60 kg/mol) structures (linear branched). We found that vitro vivo cell internalization transfection efficiency is dependent on variation polycation Mw structure, well intrinsic properties such charge ratio (R=[N + ]/[P − ]). A relation between percentage positive cells green fluorescent (GFP) amount internalized acid (cyanine 5-peGFP-C3) allowed revealing PEI promoting higher GFP HEK293T cells. In long term, outcome this work will be propose guidelines help design more effective, less cytotoxic non-viral gene carriers great potential new therapeutic applications.

Language: Английский

Citations

0