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【65】DNAワクチンの問題を考えるために - 大橋眞
DNAワクチンの臨床試験がいよいよ始まろうとしています。DNAワクチンには、一体どのような問題があるのでしょうか。ここでは、一般のDNAワクチンについて考えてみます。
DNAワクチンは、プロモーターというRNAへの転写を起こす遺伝子配列と目的とするタンパク質遺伝子が大腸菌プラスミドベクターに組み込まれた形をしています。このDNAワクチンは、宿主細胞に入らないとタンパク質を発現することができません。それでは、どのようにして細胞にDNAワクチンを入れるのでしょうか。そして、どの細胞にDNAワクチンをいれるのでしょうか。
実は、DNAが細胞に入る仕組みはよくわかっていません。ひとつの可能性としては、炎症部位に集まった食細胞がDNAを取り込むことが考えられます。そして、タンパク質を合成したあとに、このタンパク質を抗原提示細胞がリンパ球に情報を伝えて、Bリンパ球が抗体産生細胞になり、抗体を作り出す機構が考えられます。しかし、目的を終えたDNAが、どのような代謝経路をとるのかなど、不明な点が多く、未知の危険性を持っている可能性があるのです。
Clinical trials of DNA vaccines are about to begin. What are the problems with DNA vaccines? Here, let's consider a general DNA vaccine.
The DNA vaccine has a promoter, which is a gene sequence that causes transcription into RNA, and a target protein gene, which is integrated into an E. coli plasmid vector. This DNA vaccine cannot express proteins without entering the host cell. So how do you get a DNA vaccine into your cells? And which cell should the DNA vaccine be put in?
Actually, the mechanism by which DNA enters cells is not well understood. One possibility is that phagocytic cells gathered at the site of inflammation take up DNA. Then, after synthesizing the protein, the antigen-presenting cells transmit information to the lymphocytes, and the B lymphocytes become antibody-producing cells, which may be the mechanism for producing antibodies. However, there are many unclear points such as what kind of metabolic pathway the DNA that has finished its purpose takes, and there is a possibility that it has an unknown risk.
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