Evaluation of the stability and intratumoral delivery of foreign transgenes encoded by an oncolytic Foamy Virus vector.
Evaluation of the stability and intratumoral delivery of foreign transgenes encoded by an oncolytic Foamy Virus vector.
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DOI：
10.1038/s41417-022-00431-y
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发表时间：
2022-08
影响因子：
6.4
通讯作者：
Russell, Stephen J.
中科院分区：
文献类型：
--
作者：
Budzik, Karol M.;Nace, Rebecca A.;Ikeda, Yasuhiro;Russell, Stephen J.
泡沫状病毒是依赖于细胞周期的逆转录病毒，能够在静止的细胞中以不整合的方式持续存在，直到细胞分裂发生。这种独特的能力使他们能够靶向缓慢分裂的人类肿瘤细胞，这仍然是溶瘤病毒治疗中尚未满足的需求。我们已经报道了溶瘤泡沫病毒(OFV)载体系统的产生，并证明了它在感染缓慢分裂的癌细胞方面优于溶瘤小鼠白血病病毒载体。在本研究中，我们评估了(I)OFV携带外源转基因的能力和(Ii)这些载体在连续传代时的遗传稳定性。在体外培养的3代OFV中，可检测到胸苷激酶(TK)和诱导型caspase 9(ICasp9)的cDNAs。在体内，携带GFP、TK和iCasp9的OFV载体在皮下移植的胶质母细胞瘤中有效地增殖，并驱动转基因表达长达66天。然而，在体内，OFV载体的传播最终导致iCasp9基因的完全丢失，TK基因的轻微丢失和GFP的可忽略不计的丢失。我们的结果表明，OFV是一种很有前途的基因传递平台，小于1 kb的转基因可能最适合OFV的武装。
Foamy Viruses are cell cycle-dependent retroviruses capable of persisting unintegrated in quiescent cells until cell division occurs. This unique ability allows them to target slowly dividing human tumor cells which remains an unmet need in oncolytic virotherapy. We have previously reported the generation of oncolytic Foamy Virus (oFV) vector system and demonstrated its superiority over oncolytic Murine Leukemia Virus vectors in infecting slowly dividing cancer cells. In the present study we evaluated (i) the ability of oFV to carry foreign transgenes and (ii) the genetic stability of these vectors upon serial passage. The thymidine kinase (TK) and inducible caspase 9 (iCasp9) cDNAs could be detected in the oFV backbone for up to 3 in vitro passages. In vivo, GFP-, TK- and iCasp9- carrying oFV vectors propagated efficiently in subcutaneous xenograft glioblastoma tumors and drove transgene expression for up to 66 days. However, in vivo oFV vector spread eventually resulted in complete loss of the iCasp9 cDNA, minor loss of the TK cDNA and negligible loss of the GFP. Our results suggest that oFV is a promising gene delivery platform and that transgenes smaller than 1 kb might be most suitable for oFV arming.
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影响因子：
16.1
作者：
Karjoo Z;Chen X;Hatefi A
通讯作者：
Hatefi A
影响因子：
12.4
作者：
Perez, Omar D.;Logg, Christopher R.;Jolly, Douglas J.
通讯作者：
Jolly, Douglas J.
影响因子：
5.7
作者：
Miller, Amber;Suksanpaisan, Lukkana;Russell, Stephen J.
通讯作者：
Russell, Stephen J.
DOI：
10.3390/v5092169
发表时间：
2013-09-13
期刊：
Viruses
影响因子：
--
作者：
Kehl T;Tan J;Materniak M
通讯作者：
Materniak M
影响因子：
6.7
作者：
Han GZ;Worobey M
通讯作者：
Worobey M