What is self-amplifying mRNA?

And it is already being used in Japan and maybe soon in the US. It combines the unknown duration of effect of mRNA with the mutation-producing effects of nuclear DNA.

Here is what the Perplexity AI says. Note that it can be called self-amplifying DNA also:

Self-amplifying DNA refers to a type of DNA-based vaccine platform that combines elements of conventional DNA vaccines with the self-replicating capabilities of RNA viruses. Here are the key points about self-amplifying DNA:

1. Structure and components:

   • It is a circular double-stranded DNA molecule

• Contains a strong promoter (e.g., human cytomegalovirus immediate early promoter)

Encodes viral replicase genes, typically from alphaviruses or flaviviruses. Includes the gene of interest (GOI) encoding the vaccine antigen

• Mechanism of action:

  • After delivery into cells, the DNA is transcribed in the nucleus to produce self-amplifying RNA

• This RNA is transported to the cytoplasm where it self-replicates and produces high levels of the antigen

• The self-amplification process mimics viral infection, leading to sustained antigen production

• Advantages:

  • Combines benefits of DNA vaccines (stability, ease of production) with self-amplifying RNA technology

Requires lower doses compared to conventional DNA or mRNA vaccines

• Induces potent humoral and cellular immune responses

• More stable than RNA, simplifying storage and distribution

• Delivery methods:

  • Can be delivered as naked DNA, often using electroporation for improved cellular uptake

• Can also be formulated with lipid nanoparticles (LNPs) for enhanced delivery

• Applications:

  • Promising platform for rapid vaccine development against emerging infectious diseases

• Potential for use in therapeutic cancer vaccines and other applications

• Self-amplifying DNA, also referred to as DNA-launched replicons (DREPs), represents an innovative approach in vaccine technology that aims to combine the advantages of DNA vaccines with the potency of self-amplifying RNA systems.

I was asked to expand on this idea. I don’t want to alarm unnecessarily nor fail to alarm when appropriate. Let me give an example: how I approached the COVID mRNA vaccines before they were released.

1. I was worried about them but there were noreal data to go on

2. I assisted Dr. Sin Hang Lee in his petition (as editor) to the FDA to try and stop them in Nov 2020 on the basis that the Pfizer trials were not conducted per existing standards

3. I shared information from Dr. Patrick Whelan on my blog about problems that might be anticipated.

4. I did NOT tell people not to take them. I warned them about problem that might be anticipated.

5. Later I did warn people, once the problems became clearer, in January 2021 and later. I was one of the first to issue warnings, as soon as I could identify problems.

Looking back, I wish I had issued stronger warnings. But I had no reason to think the vaccines would be as bad as they were.

Right now I am looking at a theoretical vaccine construct. I’m worried. But I don’t know how worried to be. I have no human data. But Japanese doctors, where these vaccines are already being made and used, have warned that they are a disaster.

How big a disaster, I don’t know. I hope to find out in September when I will be in Japan, speaking at the ICS 6 Conference in Tokyo with the Japanese doctors who are speaking out, if not before.

And now we learn that CSL Sequirus is involved in the Japanese vaccine. BTW, 6 cases of chest pain in 828 subjects shortly after vaccination were blown off by the investigators. The control vaccine was Comirnaty, which would (naturally) make comparator vaccines look not too bad.

Here is the rest of this press release:

The approval is based on positive clinical data from several ARCT-154 studies, including an ongoing 16,000 subject efficacy study performed in Vietnam as well as a Phase 3 COVID-19 booster trial, which achieved higher immunogenicity results and a favorable safety profile compared to a standard mRNA COVID-19 vaccine comparator.  Initial study results have been published in MedRxiv and are expected to be published in a peer-reviewed journal by the end of the year.

[Here is the preprint: https://www.medrxiv.org/content/10.1101/2023.07.13.23292597v1]

"We are proud of the role that Arcturus has played in this collaboration to develop and validate the first approved sa-mRNA product in the world," said Joseph Payne, Chief Executive Officer of Arcturus Therapeutics. "This approval for the sa-mRNA COVID-19 vaccine is a major achievement, and we are excited to embark on future endeavors that utilize our innovative sa-mRNA vaccine platform alongside our global exclusive partner, CSL." 

CSL's vaccine business, CSL Seqirus, one of the largest influenza vaccine providers in the world, partnered exclusively with Meiji Seika Pharma for distribution of the sa-mRNA COVID vaccine, ARCT 154, in Japan.

"Our expertise in seasonal and pandemic influenza positions us well to help the global community reduce the burden of COVID-19 and we look forward to playing a key role in helping protect the people of Japan," said Stephen Marlow, Senior Vice President and General Manager of CSL Seqirus.

About sa-mRNA
Messenger RNA (mRNA) vaccine technology protects against infectious diseases by instructing cells in the body to make a specific protein, stimulating the immune response, and leaving a blueprint to recognize and fight future infection. However, sa-mRNA makes copies of the mRNA which generates the production of more protein compared to an equivalent amount of mRNA in a vaccine.  The technology has the potential to create more potent cellular immune responses and increase duration of protection, while using considerably lower doses of mRNA. 

About CSL
CSL (ASX:CSL; USOTC:CSLLY) is a global biotechnology company with a dynamic portfolio of lifesaving medicines, including those that treat haemophilia and immune deficiencies, vaccines to prevent influenza, and therapies in iron deficiency and nephrology. Since our start in 1916, we have been driven by our promise to save lives using the latest technologies. Today, CSL – including our three businesses: CSL Behring, CSL Seqirus and CSL Vifor – provides lifesaving products to patients in more than 100 countries and employs 32,000 people. Our unique combination of commercial strength, R&D focus and operational excellence enables us to identify, develop and deliver innovations so our patients can live life to the fullest. For inspiring stories about the promise of biotechnology, visit CSLBehring.com/Vita and follow us on Twitter.com/CSL. For more information about CSL, visit www.CSL.com.

About Arcturus Therapeutics
Founded in 2013 and based in San Diego, California, Arcturus Therapeutics Holdings Inc. (Nasdaq: ARCT) is a global late-stage clinical mRNA medicines and vaccines company with enabling technologies: (i) LUNAR^® lipid-mediated delivery, (ii) STARR^® mRNA Technology (sa-mRNA) and (iii) mRNA drug substance along with drug product manufacturing expertise. The Company has an ongoing global collaboration for innovative mRNA vaccines with CSL Seqirus, and a joint venture in Japan, ARCALIS, focused on the manufacture of mRNA vaccines and therapeutics. Arcturus' pipeline includes RNA therapeutic candidates to potentially treat ornithine transcarbamylase deficiency and cystic fibrosis, along with its partnered mRNA vaccine programs for SARS-CoV-2 (COVID-19) and influenza. Arcturus' versatile RNA therapeutics platforms can be applied toward multiple types of nucleic acid medicines including messenger RNA, small interfering RNA, circular RNA, antisense RNA, self-amplifying RNA, DNA, and gene editing therapeutics. Arcturus' technologies are covered by its extensive patent portfolio (patents and patent applications issued in the U.S., Europe, Japan, China, and other countries). For more information, visit www.ArcturusRx.com. In addition, please connect with us on Twitter and LinkedIn.