Synthetic materials at the forefront of gene delivery

Abstract

The delivery of materials for genetic engineering with transitory activity constitutes a promising field in biology and medicine with potential applications in the treatment of disease, from cancer and infectious diseases to inheritable disorders. The possibility to restore the expression of a missing protein, the potential correction of the splicing of defective genes, or the silencing or modulation of the expression of other genes constitute powerful tools that will have a great impact in the future of biology and medicine. Impressive progress has been made in the last decade, with several products reaching the market as novel technologies for gene editing emerge. However, the transference of these technologies to functional therapies is hindered by the suboptimal performance of vehicles in capturing, protecting and delivering the corresponding nucleotide cargoes with safety and efficacy.Chemistry and the chemical sciences will play a key role in the development of the innovative synthetic materials that will overcome the upcoming challenges of the next generation gene delivery therapies and protocols. In this review we address the newest chemical advances in the production of materials at the forefront of nucleotide cell delivery and gene therapy.

Glycosylated Cell‐Penetrating Peptides (GCPPs)

“…[14,16] Similaru ptake properties were found for the enantiomeric TAT [49][50][51][52][53][54][55][56][57] peptidea nd in penetrating peptoidsw ith guanidiniums ide chains anchored at the nitrogen of the amide group. [4,37,48,[50][51][52][53][54][55][56][57][58] However, despite all advances in the field, CPPs still have some limitations, mainly relatedt o their selectivity and toxicity. [17][18][19][20][21][22][23][24][25] Interesting penetrating properties were further discovered in different naturala nd artificial structures, such as polyprolines, [26] guanidinyl glycosides, [27,28] b-peptides, [29] peptiden ucleic acids (PNAs), [30] nonpeptidic guanidinylated dendritic structures, [31] self-assembled nanofibers, [32,33] synthetic polymers, [34][35][36][37] supramolecular structures, [38]…”

“…[3][4][5] More than 20 years ago, it was accidentlyd iscovered that certain protein domains, enriched in cationic amino acids, were responsible for promoting the translocation of some proteins throught he plasma membrane of cells. In 1997, Lebleu et al reportedt hat the peptidef unction of penetrating properties was attributed to the cationic domain, which was called the TATp eptide( TAT [49][50][51][52][53][54][55][56][57] ,R KKRRQRRR). In 1997, Lebleu et al reportedt hat the peptidef unction of penetrating properties was attributed to the cationic domain, which was called the TATp eptide( TAT [49][50][51][52][53][54][55][56][57] ,R KKRRQRRR).…”

“…The group of Wender at Stanford University systematically studied the TAT [49][50][51][52][53][54][55][56][57] peptide sequence and artificial analogues, and demonstrated that between eight and ten cationic amino The cell membrane regulates the exchange of molecules and information with the externale nvironment. However,t his control barrier hinders the delivery of exogenous bioactive molecules that can be appliedt oc orrect cellular malfunctions.…”

Amino Acid–Substituted Dextran‐Based Non‐Viral Vectors for Gene Delivery

“…Whereas for the in vitro use a plethora of transfection agents are commercialized, the clinical situation is limited by numerous barriers and only a limited number of non‐viral carriers reached late‐stage clinical trials. Particularly, safety concerns due to limited biocompatibility and biodegradability are one of the challenging issues that often stand against a broad therapeutic utility so far . Natural, bio‐inspired carriers present one of the highly promising solutions as they are abundantly available, sustainable, well tolerated by the body, and often biodegradable …”

EDTA‐Capped Iron Oxide Core‐Corona System as Vehicle for Gene Delivery to Transform E.coli: Mimicking the Lipid Bilayer Environment

“…that they come across during the journey in the cytosol. Lot of efforts has been made in the direction of development of safer and efficient non‐viral vectors . Amongst them, lipid based (liposomes) and polymer based (polymersomes) are the major ones.…”