Gene therapy, which treats disease by inserting, deleting, or replacing genes, relies on gene delivery vectors. Polymeric gene vectors are alternatives to viral and lipid-based vectors and are less expensive to produce, more easily modified, and, importantly, safer.

Xiu. et al. explored promising advancements in polymeric vectors and their delivery mechanisms, molecular designs, and applications.

Polymeric vectors use polymers to deliver genes, either by physically encapsulating the genes or through the electrostatic interaction between the positively charged polymers and negatively charged genes.

Transporting the gene is only part of the vectors’ job; it must also enter the cell membrane and deposit the gene intact. One promising mechanism is endocytosis, where the positively charged polymer attracts the negatively charged cell membrane, causing it to deform to encapsulate and pull the vector into the cell. The vector then escapes the encapsulating membrane and deposits the gene.

Because the polymers are specially engineered, molecular designs can be tailored to overcome specific challenges like gene uptake, gene release, and preservation of gene bioactivities.

Unlike viral and lipid-based vectors, polymeric vectors are safer in general because they do not trigger a strong immune response, integrate into the genome, or insert into the cell membrane.

Still, challenges remain for polymeric gene vectors.

“The in vivo environment, where numerous proteins, enzymes, cells, and small molecules are present, could negatively affect the transfection efficiency of some polymeric gene vectors,” said author Peter Ma.

With improved transfection efficiency, polymeric gene vectors are a promising solution to treat otherwise difficult-to-cure diseases.

“New applications such as gene editing and tissue engineering open exciting new avenues for polymeric gene vectors,” Ma said.

Source: “Recent progress in polymeric gene vectors: Delivery mechanisms, molecular designs, and applications,” by Kemao Xiu, Jifeng Zhang, Jie Xu, Y. Eugene Chen, and Peter X. Ma, Biophysics Reviews (2023). The article can be accessed at