Functional analysis of mutations endowing rAAV2-retro with retrograde tracing capacity

Zhang, Yujing; Wang, Jingyi; Li, Jiamin; Chen, Yefei; Li, Yuantao; Sun, Jing; Lu, Zhonghua; Liu, Taian

doi:10.1016/j.neulet.2022.136746

Cited by 4 publications

(7 citation statements)

References 19 publications

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“…Administration of the decoy-expressing AAV2.retro and AAV6.2 vectors by i.n. instillation suppressed virus replication in the lungs for at least 60 d. The AAV2.retro vector was somewhat more effective in suppressing virus replication than the AAV6.2 vector, which was surprising, as its capsid was selected for CNS tropism and retrograde transport in neurons ( 33 , 34 ); its tropism for the respiratory tract has not, to our knowledge, been previously described. The tropism of the AAV2.retro vector for both lung and neuronal cells could be advantageous as a means to suppress SARS-CoV-2 replication both in the respiratory tract and in olfactory tissues.…”

Section: Discussionmentioning

confidence: 87%

“…AAV2 and AAV6 are reported to have tropism for mouse and human lung and airway cells ( 30 – 32 ). AAV2.retro is an AAV2 variant that was selected for increased central nervous system (CNS) tropism and retrograde transport in axons ( 33 , 34 ). It has not been reported to transduce lung cells but in pilot experiments, we found that it worked surprisingly well.…”

Section: Resultsmentioning

confidence: 99%

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Vectored immunoprophylaxis and treatment of SARS-CoV-2 infection in a preclinical model

Tada

Minnee

Landau

2023

Proc. Natl. Acad. Sci. U.S.A.

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Vectored immunoprophylaxis was first developed as a means of establishing engineered immunity to HIV using an adenoassociated viral vector expressing a broadly neutralizing antibody. We applied this concept to establish long-term prophylaxis against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a mouse model using adenoassociated virus and lentiviral vectors expressing a high-affinity angiotensin-converting enzyme 2 (ACE2) decoy. Administration of decoy-expressing (adenoassociated virus) AAV2.retro and AAV6.2 vectors by intranasal instillation or intramuscular injection protected mice against high-titered SARS-CoV-2 infection. AAV and lentiviral vectored immunoprophylaxis was durable and was active against SARS-CoV-2 Omicron subvariants. The AAV vectors were also effective therapeutically when administered postinfection. Vectored immunoprophylaxis could be of value for immunocompromised individuals for whom vaccination is not practical and as a means to rapidly establish protection from infection. Unlike monoclonal antibody therapy, the approach is expected to remain active despite continued evolution viral variants.

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Section: Discussionmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Vectored immunoprophylaxis and treatment of SARS-CoV-2 infection in a preclinical model

Tada

Minnee

Landau

2023

Proc. Natl. Acad. Sci. U.S.A.

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“…In a parallel approach, we injected the retrograde tracer rAAV2.retro 29, 31, 43 , carrying the Cre recombinase (rAAV2.retro-hSyn- Cre ), into the right BLA of an Ai-14 mouse (Fig. 1c).…”

Section: Resultsmentioning

confidence: 99%

Monosynaptically-interconnected Network Module (MNM) Approach for High-Resolution Brain Sub-Network Analysis

Kim,

Ujihara

et al. 2024

Preprint

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We introduce the Monosynaptically-interconnected Network Module (MNM) approach, an innovative method designed for efficiently analyzing the anatomical structure and functional dynamics of specific brain network modulesin vivo. Utilizing an Intein-mediated split-Cre system combined with bidirectional adeno-associated viruses, this technique precisely targets and manipulates monosynaptically interconnected modular subnetworks in freely moving animals. We demonstrate its utility through anatomical and functional mapping of a specific MNM encompassing the prefrontal cortex (PFC), basolateral amygdala (BLA), and intermediary hub regions. Specifically, the MNM approach with Cre-reporter mice visualizes detailed network architecture and enables the tracing of axonal connections among the nodes in the network. Furthermore, integration of the MNM approach with Cre-dependent Ca2+indicator and multi-fiber photometry in freely moving mice reveals enhanced correlative network activities in social contexts. This versatile technique offers significant potential for advancing our understanding of network functions that underlie complex behaviors, providing a modular network perspective.

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“…The effectiveness of i.n. administration of the AAV2.retro vector, which was somewhat greater than the AAV6.2 vector, was surprising as its capsid was selected for high efficiency transduction of the CNS and retrograde transport in neurons 34,35 ; its tropism for the respiratory tract has not, to our knowledge, been previously described. The tropism of the AAV2.retro vector for lung and neuronal cells could be clinically advantageous as a means to suppress SARS-CoV-2 replication in respiratory and olfactory tissues.…”

Section: Discussionmentioning

confidence: 99%

“…AAV2 and AAV6 are reported to have tropism for cells of the mouse and human lung and airway [31][32][33] . AAV2.retro is a variant of AAV2 that was selected for increased tropism for the central nervous system (CNS) and retrograde movement in axons 34,35 . It has not been reported to transduce lung cells but in pilot experiments, we found that it worked surprisingly well (not shown).…”

Section: Decoy-expressing Aav Vectors Inhibit Sars-cov-2 Infectionmentioning

confidence: 99%

Vectored Immunoprophylaxis and Treatment of SARS-CoV-2 Infection

Tada

Dcosta

Minnee

et al. 2023

Preprint

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Vectored immunoprophylaxis was first developed as a means to establish engineered immunity to HIV through the use of an adeno-associated viral vector expressing a broadly neutralizing antibody. We have applied this concept to establish long-term prophylaxis against SARS-CoV-2 by adeno-associated and lentiviral vectors expressing a high affinity ACE2 decoy receptor. Administration of decoy-expressing AAV vectors based on AAV2.retro and AAV6.2 by intranasal instillation or intramuscular injection protected mice against high-titered SARS-CoV-2 infection. AAV and lentiviral vectored immunoprophylaxis was durable and active against recent SARS-CoV-2 Omicron subvariants. The AAV vectors were also effective when administered up to 24 hours post-infection. Vectored immunoprophylaxis could be of value for immunocompromised individuals for whom vaccination is not practical and as a means to rapidly establish protection from infection. Unlike monoclonal antibody therapy, the approach is expected to remain active despite continued evolution viral variants.

show abstract

Functional analysis of mutations endowing rAAV2-retro with retrograde tracing capacity

Cited by 4 publications

References 19 publications

Vectored immunoprophylaxis and treatment of SARS-CoV-2 infection in a preclinical model

Vectored immunoprophylaxis and treatment of SARS-CoV-2 infection in a preclinical model

Monosynaptically-interconnected Network Module (MNM) Approach for High-Resolution Brain Sub-Network Analysis

Vectored Immunoprophylaxis and Treatment of SARS-CoV-2 Infection

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