EIKLEIN has entered the field of gene pharmacy for many years and has rich experience in gene pharmacy. Among them, small nucleic acid drugs are the most.
Small nucleic acid drugs mainly include antisense oligodeoxynucleotides (ASO), small interference RNA (siRNA), micro RNA (miRNA), small activation RNA (saRNA), messenger RNA (mRNA), RNA adaptation (Aptamer) and so on.
Unlike small molecular chemical drugs and antibody drugs, small nucleic acid drugs are composed of nucleotides.
At present, the main categories of micronucleic acid drugs in the world are ASO, siRNA, mRNA and Aptamer.
The biggest problem in the development of small nucleic acid drugs is to avoid rapid degradation and enter targeted cells to perform therapeutic functions.
At present, there are quite mature technologies at home and abroad. with the development of gene sequencing technology, the cost of sequencing is reduced, which provides the possibility for the industrialization of small nucleic acid drugs.
The biggest difficulty in the development of small nucleic acid drugs is how to retain the drugs in the body for a long time and accurately enter the targeted cells to play a therapeutic function after injecting small nucleic acid drugs into patients, and at the same time avoid accidental injury to normal cells to the greatest extent.
Small nucleic acid drugs are unstable in the body, easy to be degraded by nuclease after entering the blood, and easy to clear through the kidney, with a short half-life. At the same time, exogenous nucleic acid molecules have immunogenicity and are easy to cause immune response of the human body.
In addition, if you can not enter the cell to achieve endocytosis, small nucleic acid drugs will not work.
These problems can be solved through chemical modification and delivery systems.
With technological breakthroughs, some difficult problems have been well solved at present. Among them, chemical modification (such as phosphate skeleton, ribose, ribose five-membered ring modification, base, nucleotide scavenging terminal modification, etc.) can prevent nucleic acid drugs from being degraded by nuclease and prolong the half-life.
Efficient and safe delivery systems (such as cyclodextrin nanoparticles, lipid nanoparticles, conjugate delivery system, acetylgalactosamine system, etc.) can make nucleic acid drugs accurately target target cells and improve cell uptake efficiency. make nucleic acid drugs play a therapeutic role.
The treatment of small nucleic acid drugs at the post-transcriptional level can achieve breakthroughs against special protein targets that are difficult to be prepared, and is expected to overcome diseases that have not yet been treated, including hereditary diseases and other refractory diseases.
Multicellularity in animals: The potential for within-organism conflict
