JP6837984B2 - 遺伝子治療用組成物 - Google Patents
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- A—HUMAN NECESSITIES
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Description
また、前記アポトーシス誘導遺伝子は、p53の遺伝子、FUS−1の遺伝子、TRAILの遺伝子およびIL−24の各遺伝子の含有量が等量である構成である。
また、前記アポトーシス誘導遺伝子は、MDM2の活性化を抑制するとともにp53依存性のアポトーシス誘導の活性化を図るため、p53の遺伝子およびFUS−1の遺伝子が、TRAILの遺伝子およびIL−24の遺伝子の倍量である構成である。
また、前記アポトーシス誘導遺伝子は、p53依存性のアポトーシス誘導の活性化を図るため、p53の遺伝子が、FUS−1の遺伝子、TRAILの遺伝子およびIL−24の遺伝子の倍量である構成である。
また、前記アポトーシス誘導遺伝子は、メラノーマに対する抗腫瘍効果を得るため、IL−24の遺伝子が、p53の遺伝子、FUS−1の遺伝子およびTRAILの遺伝子の倍量である構成である。
また、前記アポトーシス誘導遺伝子は、血管新生抑制作用および放射線療法への感受性を上げるため、TRAILの遺伝子およびIL−24の遺伝子が、p53の遺伝子およびFUS−1の遺伝子の倍量である構成である。
また、前記遺伝子治療用組成物は、更にp16の遺伝子および\またはp21の遺伝子を含有し、各遺伝子の含有量が等量である構成でもある。
また、前記リポソームは、内部空洞を有する単層膜からなるとともに、該膜はリガンドが付着されたカプセル状のベクターからなり、ジオレオイルホスファチジルエタノールアミンおよびジメチルアミノエタンカルバモイルコレステロールを含有する単層薄膜の化合物からなる構成である。
更に、前記サイトカイン遺伝子は、IL−12の遺伝子またはIL−18の遺伝子からなる構成である。
1.アポトーシス誘導遺伝子として、p53、FUS−1、TRAILおよびIL−24の各遺伝子を選択したため、効果的な癌細胞のアポトーシス活性を促すことが可能となる。
2.アポトーシス誘導遺伝子として、p53、FUS−1、TRAILおよびIL−24の各遺伝子を等量に混成したため、患者に急激なインパクトを与えることなく体に慣らすことが可能になるとともに、以後の治療において混成投与する前記各遺伝子の量の見極めを行う事が可能となる。
3.アポトーシス誘導遺伝子として、p53、TRAILおよびIL−24の各遺伝子を、FUS−1の遺伝子の倍量ほど含有する構成としたため、アポトーシス誘導の活性化を図ることが可能となる。
5.アポトーシス誘導遺伝子として、p53、FUS−1およびTRAILの遺伝子を、IL−24の遺伝子の倍量ほど含有する構成としたため、p53の遺伝子に依存しないアポトーシス誘導を活性化することが可能となる。
7.アポトーシス誘導遺伝子として、FUS−1の遺伝子を、p53、TRAILおよびIL−24の遺伝子の2倍乃至5倍量ほど含有する構成としたため、MAPK経路を通じた癌細胞の増殖を抑制することが可能となる。
9.アポトーシス誘導遺伝子として、FUS−1およびIL−24の遺伝子を、p53およびTRAILの遺伝子の倍量ほど含有する構成としたため、肺癌および/または乳がんに対する抗腫瘍効果を得ることが可能となる。
11.アポトーシス誘導遺伝子として、TRAILおよびIL−24の遺伝子を、p53およびFUS−1の遺伝子の倍量ほど含有する構成としたため、血管新生抑制作用および放射線療法への感受性を上げる効果を得ることが可能となる。
13.各種遺伝子からなる遺伝子治療用組成物をリポソームからなる遺伝子治療用リポソームベクターによってカプセル化したため、遺伝子治療用組成物の安定性を確保可能となるとともに、確実に標的腫瘍細胞へ遺伝子治療用組成物を送達することが可能となる。
15.遺伝子治療用組成物として、更に癌原遺伝子をプラスミド化した遺伝子と、サイトカイン遺伝子とからなる構成としたため、腫瘍細胞の増殖を抑制し、アポトーシスを誘導することが可能となる。
17.超音波照射処理によって懸濁液からリポソームを形成するため、200nm程度のサイズのリポソームを形成することが可能となる。
図1は、アポトーシス誘導遺伝子の組み合わせを示す一覧である。
遺伝子治療用リポソームは、混合工程と、被膜生成工程と、真空工程と、再懸濁工程と、培養工程と、超音波工程と、形成工程とからなる。混合工程は、ジオレオイルホスファチジルエタノールアミンおよびジメチルアミノエタンカルバモイルコレステロールをクロロホルム中で混合して脂質溶液を生成する工程である。これにより脂質溶液が生成される。
Claims (3)
- 抗腫瘍遺伝子がアポトーシス誘導遺伝子からなる、癌の予防および/または治療用の遺伝子治療用組成物において、
前記アポトーシス誘導遺伝子は、p53の遺伝子、FUS−1の遺伝子、TRAILの遺伝子およびIL−24の遺伝子からなるとともに、MAPK経路を通じた癌細胞の増殖を抑制するため、p53の遺伝子、TRAILの遺伝子およびIL−24の遺伝子が等重量であるとともに、FUS−1の遺伝子がそれらの2倍の重量比からなり、癌細胞をターゲットとするカチオン性脂質およびヘルパー脂質のリポソームからなる遺伝子治療用リポソームベクターによってカプセル化されるものであり、
前記リポソームは、内部空洞を有する単層膜からなるとともに、該膜はリガンドが付着されたカプセル状のベクターからなり、ジオレオイルホスファチジルエタノールアミンおよびジメチルアミノエタンカルバモイルコレステロールを含有する単層薄膜の化合物からなることを特徴とする遺伝子治療用組成物。 - 前記遺伝子治療用組成物は、更にp16の遺伝子および\またはp21の遺伝子を含有したことを特徴とする請求項1に記載の遺伝子治療用組成物。
- 前記遺伝子治療用組成物は、更に、癌原遺伝子をプラスミド化した遺伝子と、サイトカイン遺伝子とからなり、前記サイトカイン遺伝子は、IL−12の遺伝子またはIL−18の遺伝子からなることを特徴とする請求項1または請求項2に記載の遺伝子治療用組成物。
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