Abstract
Although a variety of oncolytic viruses under clinical investigation have proven to be safe, the overall efficacy of oncolytic viruses as monotherapies has been suboptimal. While responses to combination therapies are much more promising, the development of oncolytic virus monotherapies with enhanced potency is imperative. With this initiative comes the need for improved mechanisms of virus targeting to prevent off-target toxicities. MicroRNA-detargeting has emerged as an invaluable tool for preventing unwanted toxicities of oncolytic viruses, particularly for picornaviruses. Here we describe methods to test the genetic stability of microRNA response elements in vitro and to evaluate the detargeting efficiency and therapeutic index of a microRNA-detargeted picornavirus in vivo. Although the methods described herein are specific to picornaviruses, microRNA-detargeting and these assays can be adapted for different classes of oncolytic viruses.
| Original language | English (US) |
|---|---|
| Title of host publication | Methods in Molecular Biology |
| Publisher | Humana Press Inc. |
| Pages | 77-94 |
| Number of pages | 18 |
| DOIs | |
| State | Published - Jan 1 2020 |
Publication series
| Name | Methods in Molecular Biology |
|---|---|
| Volume | 2058 |
| ISSN (Print) | 1064-3745 |
| ISSN (Electronic) | 1940-6029 |
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Keywords
- Genetic stability
- MicroRNA
- Oncolytic picornavirus
- Targeting
- Virotherapy
ASJC Scopus subject areas
- Molecular Biology
- Genetics
Cite this
Insert Stability and In Vivo Testing of MicroRNA-Detargeted Oncolytic Picornaviruses. / Schulze, Autumn J.
Methods in Molecular Biology. Humana Press Inc., 2020. p. 77-94 (Methods in Molecular Biology; Vol. 2058).Research output: Chapter in Book/Report/Conference proceeding › Chapter
}
TY - CHAP
T1 - Insert Stability and In Vivo Testing of MicroRNA-Detargeted Oncolytic Picornaviruses
AU - Schulze, Autumn J.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Although a variety of oncolytic viruses under clinical investigation have proven to be safe, the overall efficacy of oncolytic viruses as monotherapies has been suboptimal. While responses to combination therapies are much more promising, the development of oncolytic virus monotherapies with enhanced potency is imperative. With this initiative comes the need for improved mechanisms of virus targeting to prevent off-target toxicities. MicroRNA-detargeting has emerged as an invaluable tool for preventing unwanted toxicities of oncolytic viruses, particularly for picornaviruses. Here we describe methods to test the genetic stability of microRNA response elements in vitro and to evaluate the detargeting efficiency and therapeutic index of a microRNA-detargeted picornavirus in vivo. Although the methods described herein are specific to picornaviruses, microRNA-detargeting and these assays can be adapted for different classes of oncolytic viruses.
AB - Although a variety of oncolytic viruses under clinical investigation have proven to be safe, the overall efficacy of oncolytic viruses as monotherapies has been suboptimal. While responses to combination therapies are much more promising, the development of oncolytic virus monotherapies with enhanced potency is imperative. With this initiative comes the need for improved mechanisms of virus targeting to prevent off-target toxicities. MicroRNA-detargeting has emerged as an invaluable tool for preventing unwanted toxicities of oncolytic viruses, particularly for picornaviruses. Here we describe methods to test the genetic stability of microRNA response elements in vitro and to evaluate the detargeting efficiency and therapeutic index of a microRNA-detargeted picornavirus in vivo. Although the methods described herein are specific to picornaviruses, microRNA-detargeting and these assays can be adapted for different classes of oncolytic viruses.
KW - Genetic stability
KW - MicroRNA
KW - Oncolytic picornavirus
KW - Targeting
KW - Virotherapy
UR - http://www.scopus.com/inward/record.url?scp=85071738641&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071738641&partnerID=8YFLogxK
U2 - 10.1007/978-1-4939-9794-7_5
DO - 10.1007/978-1-4939-9794-7_5
M3 - Chapter
C2 - 31486032
AN - SCOPUS:85071738641
T3 - Methods in Molecular Biology
SP - 77
EP - 94
BT - Methods in Molecular Biology
PB - Humana Press Inc.
ER -