Nonviral delivery systems for antisense oligonucleotide therapeutics

Abstract

Antisense oligonucleotides (ASOs) are an important tool for the treatment of many genetic disorders. However, similar to other gene drugs, vectors are often required to protect them from degradation and clearance, and to accomplish their transport in vivo. Compared with viral vectors, artificial nonviral nanoparticles have a variety of design, synthesis, and formulation possibilities that can be selected to accomplish protection and delivery for specific applications, and they have served critical therapeutic purposes in animal model research and clinical applications, allowing safe and efficient gene delivery processes into the target cells. We believe that as new ASO drugs develop, the exploration for corresponding nonviral vectors is inevitable. Intensive development of nonviral vectors with improved delivery strategies based on specific targets can continue to expand the value of ASO therapeutic approaches. Here, we provide an overview of current nonviral delivery strategies, including ASOs modifications, action mechanisms, and multi-carrier methods, which aim to address the irreplaceable role of nonviral vectors in the progressive development of ASOs delivery.

Polypyrimidine tract binding protein knockdown reverses depression-like behaviors and cognition impairment in mice with lesioned cholinergic neurons

“…As ASOs are simple to manufacture and easy to adjust, they are considered to have great clinical therapeutic potential ( Huang et al, 2022 ). ASO-PTB can knock down PTB at the mRNA and protein levels.…”

Amphiphilic Block Copolymer Nanostructures as a Tunable Delivery Platform: Perspective and Framework for the Future Drug Product Development

“…The recent developments focus on improving the safety profile of ASOs with the aid of suitable delivery carriers that facilitate targeted biologic drug delivery, enhanced stability, and reduced toxicities. 153 A potential polymer-based nanoparticle reported by Kolonko et al used natural amino polysaccharide chitosan (CS) to deliver ASO against epithelial sodium channel (ENaC) to the airway epithelium to circumvent Na + hyperabsorption implicated in cystic fibrosis. 154 This observation further emphasizes the potential of degradable cationic ABCPs in the context of ASO delivery.…”

“…In light of all the restrictions, the delivery platform becomes crucial for the efficient use of ASOs in various therapeutics. The recent developments focus on improving the safety profile of ASOs with the aid of suitable delivery carriers that facilitate targeted biologic drug delivery, enhanced stability, and reduced toxicities . A potential polymer-based nanoparticle reported by Kolonko et al used natural amino polysaccharide chitosan (CS) to deliver ASO against epithelial sodium channel (ENaC) to the airway epithelium to circumvent Na + hyperabsorption implicated in cystic fibrosis .…”

Biomaterial‐based gene therapy

“…33 ASOs are single-stranded nucleic acid polymers comprising 18−30 bases that can combine with specific sequences of target mRNAs through complementary base pairing to upregulate or downregulate protein expression. 34,35 Antisense RNAs comprise a class of small RNAs without coding functions of their own, but can suppress the function of target RNAs and regulate the expression of the corresponding gene by complementarily binding to the target RNA, especially to specific regions of the mRNA, through hydrogen bonds between paired bases.…”