On June 5, 2022, at 10:44 AM, China launched the Shenzhou-14 manned spacecraft from the Jiuquan Satellite Launch Center using the Long March-2F Y14 rocket, carrying astronauts Chen Dong, Liu Yang, and Cai Xuzhe into space for a six-month mission to complete various assigned tasks.

mRNA has a half-life of approximately 7 hours , a large molecular weight (10⁴–10⁶ Da) , and carries a negative charge under physiological pH conditions —making it difficult to cross the cell membrane composed of anionic lipids. It is also readily degraded by nucleases in vivo. These obstacles have hindered the delivery of mRNA into the human body and its successful translation into clinical applications. Therefore, it is also necessary to design a "rocket" —a suitable delivery system—to achieve mRNA delivery, ensuring that mRNA reaches target cells safely, is protected from nuclease degradation, and promotes cellular uptake without causing toxicity or unwanted immunogenicity.

Advances in delivery technology have greatly promoted the development and clinical application of the mRNA pharmaceutical industry. Methods for delivering mRNA include physical methods , viral vector methods , and non-viral vector methods.

Among these, electroporation and gene guns are classic physical methods for mRNA delivery, but clinical trials have shown that these methods are often harmful to cells and unsuitable for in vivo application. Currently, development strategies for mRNA delivery carriers focus on two major directions: viral vectors and non-viral vectors.

Viral vectors such as lentivirus and adeno-associated virus (AAV) have very high delivery efficiency and can ensure long-term gene expression, making them the most widely used nucleic acid delivery carriers in clinical practice. However, viral vectors have key defects—including risks associated with genomic integration , host rejection (immunogenicity and cytotoxicity) , limited payload packaging capacity, and manufacturing difficulties. These safety, stability, and efficacy issues have significantly limited the application of viral vectors in clinical use.

In contrast, non-viral vectors —as the "rocket"—can effectively protect the mRNA "astronauts" from external environmental influences or nucleases. They generally have lower immunogenicity , higher safety , are relatively convenient to design and synthesize , easy to produce , and allow repeat administration. For these reasons, they are considered ideal carriers for mRNA delivery and have developed rapidly in recent years.

Non-viral vectors mainly include liposomes , dendrimers , inorganic nanoparticles , cationic cell-penetrating peptides , and others. Liposomes and their derivatives have become the most effective non-viral vectors for mRNA delivery. The main lipid carriers used for mRNA drug delivery include lipoplexes (LP) , lipopolyplexes (LPR) , Lipid Nanoparticles (LNP) , and cationic nanoemulsions (CNE) .

Non-viral delivery systems represented by LNPs can effectively load mRNA and transfect cells, express specific antibodies, and activate immune responses—demonstrating good clinical efficacy in combating COVID-19 infection.

While the design and stability of mRNA itself are prerequisites, the efficiency of the delivery system is equally critical, as it determines the therapeutic efficacy of mRNA drugs in real-world applications. However, drug delivery is a complex problem that connects the intrinsic properties of drugs with the variable microenvironments of the human body—requiring knowledge spanning biology, materials science, chemistry, pharmacology, and medicine.

In 2020, Jennifer Doudna —who received the Nobel Prize in Physiology or Medicine for her outstanding contributions to CRISPR—once remarked: "Delivery may remain the biggest bottleneck for somatic cell gene editing."

Today, we do not know when the next unforeseeable "COVID-19" crisis will arrive. The lessons of past failures and the experience gained in the present are valuable assets for developing future drug delivery technologies. What we can and should do is to continuously accumulate success from failure —"prepare one, reserve one" , "prepare one, reserve two" , or even "prepare one, reserve three or four" —creating more innovative drug delivery technologies and always being ready for "launch" to meet current and future clinical needs.