The General Hospital Corporation

Other

The Ohio State University

Yoshinaga Saeki

Xandra O Breakefield

E Antonio Chiocca

Mark Suter

Gosse Jan Adema

Mathias Ackermann

Cornel Fraefel

Antonio Chiocca

Richard Wade-Martins

Miguel Sena-Esteves

Ken Shortman

Kurt Tobler

Malignant tumors that are intrinsically resistant to conventional therapies are significant therapeutic challenges. An embodiment of the present invention provides an oncolytic virus capable of killing target cells, such as a tumor cells. In various embodiments presented herein, the oncolytic virus is armed or encodes a therapeutic polypeptide. In at least one embodiment, a recombinant oncolytic virus has been generated that can specifically replicate in cancer cells leading to their destruction and at the same time secrete robust amounts of a therapeutic polypeptide. Compositions and methods disclosed herein have broad therapeutic applicability.

Oncolytic virus

The present invention relates to HSV-based amplicon vectors carrying a genomic DNA fragment, and methods of constructing and using the same. Included within the present invention is a method of converting any large capacity DNA cloning vector, such as a BAC or PAC, into an HSV amplicon or hybrid HSV amplicon using site-specific, or other types of recombination, so that genomic DNA inserts within the BAC or PAC clone can be delivered by infection to a cell, and efficiently expressed. The present invention also relates to a system for the rapid creation of viral vectors carrying transgenes of interest. This aspect of the invention is accomplished through recombination between: (a) a large-capacity cloning vector carrying a viral genome, and (b) a transfer vector containing the transgene of interest. Finally, an expression-ready genomic DNA library is disclosed.

Viral delivery system for infectious transfer of large genomic DNA inserts

The present invention relates to a triple hybrid vector amplicon system comprising genetic elements derived from Herpes Simplex Virus (HSV), Epstein-Barr Virus (EBV) or Adeno-Associated Virus (AAV), and a retrovirus. The vector was developed to stably transform cells, both in culture or in vivo, into retrovirus packaging cells in a single step. This step can be accomplished both by transfection using liposomes, electroporation, calcium phosphate, or any other methodology used to transfer naked or complexed DNA into cells or by infection when the vector is packaged as an amplicon vector in HSV virions.

Triple hybrid amplicon vector systems to generate retroviral packaging lines

The present invention relates to an enhanced and simplified herpes virus amplicon packaging system. The packaging system comprises a herpes virus amplicon vector and a packaging vector. In one embodiment, the packaging vector comprises a bacterial artificial chromosome (BAC) containing the HSV-1 genome. The packaging vector contains an intact pac site but is otherwise rendered packaging defective. The packaging vector can be rendered packaging defective by inserting nucleotides into the pac site, or by otherwise interfering with the capsid's ability to close, for example, by increasing the size of the DNA fragment upon which the herpes virus genome is cloned. This system can be used to package a wide range of nucleotide sequences (e.g., a therapeutic or antigenic gene) into an empty herpes virus particle taking advantage of the large transgene capacity of herpes viruses. This system can also be used as a vaccine to induce protective immunity against HSV-1, or other complex pathogens.

Enhanced packaging of herpes virus amplicons and generation of recombinant virus vectors

Growing community of inventors

Toyama, Japan

Yoshinaga Saeki