Intrastriatal Delivery of Integration-Deficient Lentiviral Vectors in a Rat Model of Parkinson’s Disease

Abstract

Standard integration-proficient lentiviral vectors (IPLVs) are effective at much lower doses than other vector systems and have shown promise in several gene therapy approaches. Their main drawback is the potential risk of insertional mutagenesis. Novel biosafety-enhanced integration-deficient lentiviral vectors (IDLVs) offer a significant improvement and comparable transduction efficacy to their integrating counterparts in some central nervous system applications. We describe here methods for (1) production of IDLVs (and IPLVs), (2) IDLV/IPLV delivery into the striatum of a rat model of Parkinson's disease, and (3) postmortem brain processing.

Gene-Editing Technologies Paired With Viral Vectors for Translational Research Into Neurodegenerative Diseases

“…Furthermore, immunohistochemistry at 1-year post-injection showed a dramatic reduction of mutant aggregates in Purkinje cells of both IDLV- and ICLV-injected SCA3 mice. Many other laboratories have also demonstrated efficient use of IDLVs for the transduction of most cell types in the brain (Saida et al, 2014 ; Lu-Nguyen et al, 2016 ; Ortinski et al, 2017 ). More recently, we established and optimized IDLV vectors as a means for safe and efficient delivery of CRISPR/Cas9 components (Ortinski et al, 2017 ; Vijayraghavan and Kantor, 2017 ).…”

Study of subchronic toxicity of the developed antibacterial drug based on exosomal particles

“…In our opinion, the most promising is the use of biodegradable delivery systems, due to their low toxicity and xenobiotic effects on the patient's body [1,2,3]. The development of biocompatible nanostructured drugs is an integral part of modern veterinary medicine [4][5][6][7][8]. The need to develop regulated drug delivery systems is conditioned by their clear therapeutic advantage over analogues in standardized dosage forms [9][10][11][12][13].…”