US 12,203,092 B2
Self-inactivating rabies virus vector encoding a nucleoprotein and degron
Marco Tripodi, Cambridge (GB); and Ernesto Ciabatti, Cambridge (GB)
Assigned to Mironid Limited, North Lanark (GB)
Appl. No. 16/607,980
Filed by United Kingdom Research and Innovation, Swindon (GB)
PCT Filed May 2, 2018, PCT No. PCT/GB2018/051166
§ 371(c)(1), (2) Date Oct. 24, 2019,
PCT Pub. No. WO2018/203049, PCT Pub. Date Nov. 8, 2018.
Claims priority of application No. 1706945 (GB), filed on May 2, 2017.
Prior Publication US 2021/0115472 A1, Apr. 22, 2021
Int. Cl. C12N 15/86 (2006.01); C07K 14/145 (2006.01); A61K 38/00 (2006.01)
CPC C12N 15/86 (2013.01) [C07K 14/145 (2013.01); A61K 38/00 (2013.01); C07K 2319/50 (2013.01); C07K 2319/95 (2013.01); C12N 2760/20143 (2013.01); C12N 2770/00022 (2013.01); C12N 2810/609 (2013.01)] 29 Claims
 
1. A rabies virus vector genome comprising a gene encoding a replication modulator protein,
wherein the replication modulator protein comprises a viral protein moiety which is required for replication of the viral genome, and a regulator moiety,
wherein the viral protein moiety is a rabies virus N (nucleoprotein) protein, wherein the regulator moiety comprises a protease cleavage site and a degron, wherein the degron is a PEST sequence, and wherein the protease cleavage site is located between the viral protein moiety and the degron,
wherein the replication modulator protein is capable of adopting a targeted configuration displaying the degron, and an untargeted configuration which does not display the degron, and
wherein the replication modulator protein is an inhibitory modulator switchable to the untargeted configuration on contact with a cognate activating agent, wherein the cognate activating agent is a protease, and wherein said vector is transcriptionally silent in the absence of the protease and transcriptionally active in the presence of the protease.