Development of a Recombinant Multifunctional Biomacromolecule for Targeted Gene Transfer to Prostate Cancer Cells

Abstract

The objective of this study was to genetically engineer a fully functional single chain fusion peptide composed of motifs from diverse biological and synthetic origins that can perform multiple tasks including DNA condensation, cell targeting, cell transfection, particle shielding from immune system and effective gene transfer to prostate tumors. To achieve the objective, a single chain biomacromolecule (vector) consisted of four repeatative units of histone H2A peptide, fusogenic peptide GALA, short elastin-like peptide and PC-3 cell targeting peptide was designed. To examine the functionality of each motif in the vector sequence, it was characterized in terms of size and zeta potential by Zetasizer, PC-3 cell targeting and transfection by flowcytometry, IgG induction by immunogenicity assay and PC-3 tumor transfection by quantitative live animal imaging. Overall, the results of this study showed the possibility of using genetic engineering techniques to program various functionalities into one single chain vector and create a multifunctional non-immunogenic biomacromolecule for targeted gene transfer to prostate cancer cells. This proof-of-concept study is a significant step forward towards creating a library of vectors for targeted gene transfer to any cancer cell type at both in vitro and in vivo levels.

Nanoparticles-based delivery system and its potentials in treating central nervous system disorders

“…The fusion peptide method does not simply involve the sum of multiple independent functions. The enhancement of specific functions and even novel property generation have been reported [97]. In a recent study, a BBB-penetrating peptide TGN was integrated into the neuron-targeting peptide Tet 1 to form an optimized fusion peptide through a four-glycine linker [98].…”

Revival of Bioengineered Proteins as Carriers for Nucleic Acids

“…The simplicity of AOCs makes them readily adaptable, while the pool of available antibodies continuously expands. , Since 2022, various AOCs entered phase 2 clinical trials for a variety of indications, such as myotonic dystrophy type 1. , The principle of targeting carriers via antibodies and receptor-specific peptides is not limited to the delivery of oligonucleotides. Incorporation of these targeting moieties also showed increased cellular uptake and cell specificity for protein-based DNA and mRNA carriers. − To enable cytoplasmic delivery multiple studies exploited the ability of pore-forming proteins to connect the endosomal lumen to the cytosol. ,, For example, Wittrup et al, employed pore-forming perfringolysin O (PFO) as a potent endosomal escape agent in their protein-based siRNA carrier . The carrier complexed siRNA via the double-stranded RNA (dsRNA) binding domain of human protein kinase R. Efficient cellular uptake was achieved by fusion with engineered 10th type 3 fibronectin (Fn3).…”

Development of a ZHER3‐Affibody‐Targeted Nano‐Vector for Gene Delivery to HER3‐Overexpressed Breast Cancer Cells

“…The design and generation of efficient carriers for gene transfer into specific cells have attracted much interest in recent years . In recent years, several research groups have designed and produced various recombinant peptide‐based vectors in order to deliver specific genes into cancer cells . It has been demonstrated that these kinds of peptides do not cause a severe immune response .…”

“…[32] In recent years, several research groups have designed and produced various recombinant peptide-based vectors in order to deliver specific genes into cancer cells. [33][34][35][36][37][38][39] It has been demonstrated that these kinds of peptides do not cause a severe immune response. [40,41] In addition, they were extensively applied to several applications due to the ease of the use and production in large scale.…”