Cationic Liposome and Gene Therapy

Gene therapy refers to the introduction of foreign normal gene sequences into target cells to
replace defective DNA sequences in patients and to correct or compensate for diseases
caused by gene defects and abnormalities, thus achieving the goal of treatment. In the
process of gene therapy, a key step is to construct a gene vector, and deliver the exogenous
DNA sequence to the target cell through the gene vector for efficient transfection and
expression. The methods of transducing the gene of interest applied so far can be divided
into two broad categories: viral vectors and non-viral vectors. As a highly efficient gene
delivery system, viral vector has the advantages of high transfection and high expression
efficiency, and is one of the most effective tools for efficient expression of foreign genes in
vivo. However, due to its high immunogenicity, small capacity, difficulty in preparation,
damage to target organs, and high production cost, its application in gene therapy is limited.
Compared with viral vectors, non-viral vectors have become a common carrier in gene
transfer in recent years due to their advantages of simple preparation, low toxicity, low
immunogenicity and biodegradability. Cationic liposome, as the most studied carrier in non-
viral vectors, has broad prospects in gene therapy

Structural features of liposomes and cationic liposomes

Liposomes consist of phospholipids and other lipids with biofilm-like structure. In water, this
structure disperses to form multi-layered microcapsules, each of which is a liposome. The
cationic liposome formed by a positively charged amphoteric compound and a neutral lipid.
Cationic lipid, also known as cell transfectin SU, are the core site of cell transfection by cationic
liposomes. The basic structure of cationic lipids is that a positively charged group is attached
to a hydrophobic group, and the positive charges carried by cationic lipids can interact with
the negative charges on the target gene to form stable complexes and increase the cycle time
in the body. The most common cationic groups are ammonium, imidazole and lysine.

Cationic liposome-mediated gene transfer mechanism

As a gene carrier, a brief description of the cationic liposome-mediated gene transfer process
is : a positively charged cationic liposome and a negatively charged target gene (DNA or RNA)
sequence are attracted to each other by electrostatic interaction to form DNA / cationic
liposome complex, which can enter the cell through endocytosis or membrane fusion, and
the lipid complex releases genes in the cytoplasm or further into the nucleus to complete
intracellular transcription and translation.

Advantages of cationic liposome in gene therapy

Compared with traditional medical treatments, such as surgery and chemotherapy, gene
therapy as a breakthrough targeted biological gene therapy method has the advantages of
strong pertinence, no side effects and no damage to normal cells. Gene vector is one of the
key technologies in gene therapy, which can protect genes from degradation by endogenous
nucleases, thus making it possible to apply gene therapy in vivo. At present, gene vectors
used in gene therapy are mainly viral vectors and non-viral vectors. As a non-viral vector,
cationic liposomes have the following advantages over viral vectors:
① Protection of therapeutic genes from degradation in vivo circulation.
② Specific targeted delivery of genes to target tissues or cells.
③ Transfect cells efficiently through cell membrane and nuclear membrane to express /
silence genes.

Outlook
Cationic liposome, as a new drug carrier, has the advantages of targeting, long - acting, low
toxicity and protecting drugs. Its appearance has brought new dawn to many research fields.
With the successful development of targeted liposomes and other new lipids, drugs or genetic
materials are delivered directly to diseased tissues or organisms, making treatment more
specific and efficient. However, how to transfer genetic materials or drugs more efficiently is
still a huge challenge. In order to solve the above problems, the newly developed anion-
cation liposome neutralizes part of the positive charge on the surface of the cation liposome
in recent years, weakening the cytotoxicity of the cation liposome and increasing the cycle
time of the complex in vivo to a certain extent. The anion liposome itself has certain
cytotoxicity, which cannot be avoid. Therefore, improving the stability, targeting and
transfection efficiency of cationic liposomes, modifying the surface of cationic liposomes,
inventing and using new preparation techniques, and clarify the detailed mechanism of
cationic liposome-mediated gene transfection from the perspective of molecular biology will
be the focus of future research.

About author
Creative Biostructure is an innovative biotechnology company founded in 2005, which has
committed to the research and development of liposome technology in the past decade.