LNP GENE-THERAPY

Lipid nanoparticle (LNP)-formulated small interfering RNA (siRNA) or gene editor, such as CRISPR-Cas9 and base editors, has recently emerged as efficient and clinically proven approaches in the molecular targeting of disease-driver genes. LNP-formulated siRNA or in vivo gene-editing has multiple advantages over traditional therapeutics in cancer therapy, providing the driver-gene is known (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. Recently, LNP-dependent delivery of the nuclease Cas9 and single guide RNA targeting TTR reduced serum levels of transthyretin by 87% in patients in a breakthrough phase 1 clinical trial. Antapodia Therapeutics harnesses the third-generation highly biodegradable LNPs in conjunction with a novel "liver-blocking" technology to efficiently deliver invadopodia-targeted siRNA and base editors to hepatic or non-hepatic 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 therapeutics

 

Specificity

Potential toxicity

Tissue penetration

Intracellular targeting

Duration of effects

Clinically proven

LNP-siRNA Very high Very low High Yes 4-7 days 3 FDA approvals1
microRNA Low Medium-to-high 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
LNP-gene editing Very high Very low High Yes Permanent 1 (phase 1)3 

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

2Desmoplastic cancers

3Gillmore JD, et al. CRISPR-Cas9 in vivo gene editing for transthyretin amyloidosis. New Engl J Med 2021.

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Designed by Justin V. Tsai in 2021

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

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