top of page

Sachi's NanoligomerTM platform can deliver to the brain with systemic administration

Brain delivery of Nanoligomer using systemic administration

What if you could deliver RNA therapeutics to the brain for high-precision gene-targeting? Serving a long time need in the industry, Sachi Bio has done just that, with the proprietary technology called NanoligomersTM. In a published study, it was shown that Nanoligomers can reduce inflammation in mice brain significantly in less than a week. These results have important implications of range of neuroinflammatory and neurological diseases including Alzheimer's disease, Parkinson's disease, Multiple sclerosis.

Checkout the publication: "Identifying an Optimal Neuroinflammation Treatment Using a Nanoligomer Discovery Engine." Sadhana Sharma, Curtis Borski, Jessica Hanson, Micklaus A. Garcia, Christopher D. Link, Charles Hoeffer, Anushree Chatterjee, and, Prashant Nagpal *, ACS Chem. Neurosci.2022, 13, 23, 3247–3256.

Why this matters to patients?

Accessing the brain has been difficult. Previous attempts with RNA therapy have been challenging. Gene-targeting using RNA therapeutics opens up a new window towards creating precision treatments for patients. However, delivery of RNA therapeutics to targeted tissues has been shown to be a difficult challenge in the past.

Sachi Bio has been working diligently on this challenge to develop a RNA therapeutic technology that can target disease-causing genes, while being easily delivered into the brain.

Opening window to a new paradigm

This opens the possibility of targeting disease-causing genes, and identifying key mechanisms and disease pathways that could not be targeted before. Many interesting drug targets are often undruggable using conventional therapeutic technologies. This is not a challenge for RNA therapeutics. To be able to target genes and pathways with precision, and deliver to the correct organ, will de-risk the entire drug discovery and development process.


​Sadhana Sharma, Curtis Borski, Jessica Hanson, Micklaus A. Garcia, Christopher D. Link, Charles Hoeffer, Anushree Chatterjee, and ,Prashant Nagpal* (2022). ACS Chemical Neuroscience 2022, 13, 23, 3247–3256.

Abstract and Link to the paper:

Acute activation of innate immune response in the brain, or neuroinflammation, protects this vital organ from a range of external pathogens and promotes healing after traumatic brain injury. However, chronic neuroinflammation leading to the activation of immune cells like microglia and astrocytes causes damage to the nervous tissue, and it is causally linked to a range of neurodegenerative diseases such as Alzheimer’s diseases (AD), Multiple Sclerosis (MS), Parkinson’s disease (PD), and many others. While neuroinflammation is a key target for a range of neuropathological diseases, there is a lack of effective countermeasures to tackle it, and existing experimental therapies require fairly invasive intracerebral and intrathecal delivery due to difficulty associated with the therapeutic crossover between the blood-brain barrier, making such treatments impractical to treat neuroinflammation long-term. Here, we present the development of an optimal neurotherapeutic using our Nanoligomer Discovery Engine, by screening downregulation of several proinflammatory cytokines (e.g., Interleukin-1β or IL-1β, tumor necrosis factor-alpha or TNF-α, TNF receptor 1 or TNFR1, Interleukin 6 or IL-6), inflammasomes (e.g., NLRP1), key transcription factors (e.g., nuclear factor kappa-B or NF-κβ) and their combinations, as upstream regulators and canonical pathway targets, to identify and validate the best-in-class treatment. Using our high-throughput drug discovery, target validation, and lead molecule identification via a bioinformatics and artificial intelligence-based ranking method to design sequence-specific peptide molecules to up- or downregulate gene expression of the targeted gene at will, we used our discovery engine to perturb and identify most effective upstream regulators and canonical pathways for therapeutic intervention to reverse neuroinflammation. The lead neurotherapeutic was a combination of Nanoligomers targeted to NF-κβ (SB.201.17D.8_NF-κβ1) and TNFR1 (SB.201.18D.6_TNFR1), which were identified using in vitro cell-based screening in donor-derived human astrocytes and further validated in vivo using a mouse model of lipopolysaccharide (LPS)-induced neuroinflammation. The combination treatment SB_NI_111 was delivered without any special formulation using a simple intraperitoneal injection of low dose (5 mg/kg) and was found to significantly suppress the expression of LPS-induced neuroinflammation in mouse hippocampus. These results point to the broader applicability of this approach towards the development of therapies for chronic neuroinflammation-linked neurodegenerative diseases, sleep countermeasures, and others, and the potential for further investigation of the lead neurotherapeutic molecule as reversible gene therapy.


Commenting has been turned off.
bottom of page