Lipid nanoparticle (LNP) in nucleic acid (NA)-based vaccines and therapeutics
核酸疫苗和治療中的脂質奈米顆粒 (LNP)
Lipid nanoparticle (LNP) in nucleic acid (NA)-based vaccines and therapeutics
Lipid nanoparticle (LNP) in nucleic acid (NA)-based vaccines and therapeutics
Targeted indication
Vaccine and immunotherapy
Status
Lipid nanoparticle (LNP) in nucleic acid (NA)-based vaccines and therapeutics
Key features
- NA-LNP can be synthesized by self-assembling process using microfluidic approach.
- NA-LNP surface programmed with ABC compromises efficacy and biocompatibility.
- NA-LNP-vaccinated hamsters generate effective protection against virus challenge.
Market
- The invention describes the design of the expression sequences and increase DNA delivery by encapsulation within lipid nanoparticles without using electro-pulsed machines. The invention is more convenient, efficient and cheaper than current NA vaccines.
- The invention can be used in both prophylactic and therapeutic vaccine against different diseases. The applications include both DNA and RNA vaccines.
MODE OF ACTION
Successful DNA vaccination can be achieved with the aid of lipid nanoparticle (LNP) approach which comprises hybrid mixture of cholesterol, helper lipid, ionizable cationic lipid, and an AB-type amphiphilic bioresorbable copolymer. The rational design of DNA-LNP conciliates between stability and biocompatibility which offers new insights into COVID-19 vaccine boosters.
EXPERIMENTAL RESULTS
The content of PEGylated lipid on the prospective efficiency of LNPs.
After passing through the inlet channel of the microfluidic chip, stable nanoparticles of uniform distribution (namely DNA-LNP-FM) can be prepared. By removing the DMG-PEG, the DNA-LNP (DNA-LNP-F1) conserved the encapsulation efficiency of LNPs, while the DNA recovery rate was lower (~10%); in addition, the DNA-LNPs tended to aggregate with a broader particle size scale, polydispersity and zeta potential. Supplementation with the appropriate ingredients of PLA-PEG helps DNA-LNPs stabilize and shrink the particles as more building block components are embedded in the LNP structure. Within the 72-hour incubation of HEK293 cells with DNA-LNPs, we suggested that the selection of surface-active agents may play a crucial role in DNA-LNP-induced cell death.
LNP platform technology in COVID-19 DNA vaccine
We conducted animal experiments on the efficiency of DNA-LNP vaccines against SARS-CoV-2 and its variants. Following sequential vaccination regimen (Fig A), we found that the sera obtained from TSomi DNA-LNP-vaccinated hamsters could generate effective Omicron-specific neutralizing antibodies (Fig B, left), the Wuhan virus neutralizing antibodies were rather reduced (Fig B, right). After infection with Wuhan virus, we found that the hamsters vaccinated with TSomi DNA-LNP did not show a decrease in body weight during 6 days of monitoring at either 10 µg or 30 µg dosages; on the other hand, the hamsters that received Tris buffer alone showed a 10% reduction in body weight (Fig C). As depicted in Fig D, the viral load in the lung showed a mild reduction on Day 3 in the 10 µg DNA-LNP group compared to the buffer control, and this reduction continued to progress through Day 6; however, it is important to note that the loaded virus was not fully eradicated from the host at this dosage. Based on the pathogenesis in the lung at Day 6, the buffer control group showed severe inflammation, while very low inflammation was found in the DNA-LNP vaccination groups (Fig E,F).
INTELLECTUAL PROPERTY
SELECTED PUBLICATIONS
Molecular Therapy Nucleic Acids. 2024;35(3):102261.
BUSINESS OPPORTUNITY
License out and/or Collaboration and Sponsored Research
CONTACT
Contact BioMed Commercialization Center, TAIWAN at liupanghsi@biip-dcc.org