LNP siRNA THERAPY

Lipid nanoparticle (LNP)-formulated small interfering RNA (siRNA) has recently emerged as efficient and clinically proven approaches in the molecular targeting of disease-driver genes. LNP-formulated siRNA therapy has multiple advantages over other therapeutic modalities in cancer (Table 1). For instance, the parenteral administrations of an LNP-encapsulated siRNA specific for transthyretin (TTR) reduce up to 86.8% of transthyretin produced by the liver in patients with hereditary transthyretin-mediated amyloidosis and thus became the first clinically approved siRNA therapy. Antapodia Therapeutics harnesses the most advanced third-generation LNP (3gLNP) (Table 2) in conjunction with a breakthrough "liver-blocking" technology to efficiently deliver invadopodia-targeted siRNA to non-hepatic and metastatic cancers, resulting in tremendous anti-tumor and anti-metastasis efficacies in preclinical studies. In collaboration with academic and industrial leaders in LNPs, the company strives to develop the best-in-class cancer-gene therapies to concur aggressive and metastatic cancers.

Table 1. Comparison among different anti-cancer therapeutic modalities

 

Specificity

Potential toxicity

Tissue penetration

Intracellular targeting

Duration of effects

Clinically proven

siRNA Very high (1 target transcript)
Very low (1 gene)
High Yes 4-7 days 3 FDA approvals1
microRNA Low (>100 target genes)
Likely
High Yes 4-7 days No
Small molecules Medium-to-high Likely High Yes Varied Many
Antibody therapeutics High Low Poor2 to moderate No 2-3 weeks Many

1ONAPATTRO® (patisiran) for hereditary transthyretin-mediated amyloidosis (approved in 2018); GIVLAARI® (givosiran) for hepatic porphyria (approved in 2019); OXLUMO® (lumasiran) for primary hyperoxaluria (2020).

2For desmoplastic human solid cancers such as pancreatic cancer, prostate cancer, non-small cell lung cancer and certain breast cancer.

Table 2. Comparison among different generations of lipid nanoparticles

Ionizable lipidI

Generation

Optimized
payload

Developer

Licensee

Application

Potency Bio-
degradable
Liver toxicity1
FDA approval
KC2 1st siRNA Arbutus 0.1X Slow Likely
MC3 2nd siRNA Acuitas Alnylam Rare disease 1X Slow Likely Patisiran
ALC-0315 2nd mRNA Acuitas BioNTech Vaccine 1X Yes Low Tozinameran
SM-102
Un-
known
mRNA Moderna Moderna Vaccine Un-
known
Yes Unknown Spikevax
3gLNP
lipid
3rd

siRNA/
mRNA

Un-
disclosed
Antapodia partner
Cancer
Inflammatory

disease
~5X High Unlikely

1For repetitive intravenous administrations.

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Designed by Justin V. Tsai in 2021

Copyright © Antapodia Therapeutics, Inc., WA, USA. All Rights Reserved.

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