CRIDS - PO-Laboratories

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CRIDS: A Major Breakthrough in Antiviral Therapy, including COVID-19
COVID-19 therapy

PO-Laboratories was established in 2003 by Merck’s Senior Researcher. Over the years, PO-Laboratories attracted several brilliant scientists, including biotechnologists, microbiologists and geneticists. Such a fusion of experts resulted in the development of a revolutionary drug family called CRIDS, which works by precise targeting and the subsequent destruction of the genome of a pathogen, and this includes SARS-CoV-2 (COVID-19).
CRIDS is an interdisciplinary invention – it includes polymer science, molecular biology, drug delivery, nanotechnology and genetics.

CRIDS opens a new era of programmable drugs. CRIDS can be quickly programmed to target and selectively kill any pathogen by destroying its genome and being harmless to any other cells and organisms, including humans.

It based on a natural viral defense system found in some bacteria. Bacteria use a simple two-component system, which includes crRNA that is able to identify the virus by matching sequence and then it triggers a Cas ferment, which cuts that viral RNA or DNA, as a result killing the virus. Such bacterial defense system has a name – CRISPR.
CRISPR-Cas



Details of Antiviral Defense in Bacterias:

The so-called CRISPR-Cas system is a natural antiviral defense system discovered in many bacteria and archaea. It is a simple two-component system that includes a CRISPR-RNA or crRNA in short, and a Cas protein (a ferment, endonuclease).

If a cell is attacked by a virus and survives, the fragments of the viral genome the cell appends to its DNA.
These fragments of viral genome the cell uses to express crRNAs.  crRNA holds targeting information to a specific region in the viral genome, say “fingerprints” of the virus. Upon a secondary viral invasion, Cas protein combined with crRNA recognizes the viral genome's specific sequence and cuts it, killing the virus [1].
This sytem can be used to treat viral infections in humans and animals.
To form an antiviral drug, the crRNA have to be combined with Cas endonuclease protein and be placed inside of a human or animal cells.
Cas endonuclease combined with crRNA form so-called CRISPR complex.
crRNA holds targeting information to a specific region in the viral genome. It is a truly programmable part of the drug, because to create crRNA targeted to COVID-19, for example, there is no need to use bacteria adaptation mechanism. The crRNA targeted to COVID-19 can be easily programmed and synthesized. To do so, required a sequence of the viral genome and appropriate software.
The CRISPR complex finds viral RNA or DNA that has a sequence complementary to crRNA, and if a perfect match occurs, Cas protein cuts (cleaves) the targeted viral DNA or RNA. If the cut was made in a vital point of the genome, the virus is unable to repair itself and dies. CRISPR complex is exceptionally selective and efficient as an antiviral defense as Nature designed it. Multiple crRNAs targeted at different points in the viral genome can be used simultaneously.


DNA1
All living organisms, including bacteria and viruses, have an extremely critical vital part – genome, in the form of DNA or RNA. The genome of every organism includes unique sequences specific to this particular organism or strain.
The genome of an organism also includes sequences unique to its family. Genomes of most viruses and bacteria are known, including the genome of SARS-CoV-2 also known as COVID-19. Targeting a specific unique sequence of a virus allows it to be reliably and very selectively destroyed.

CRISPR system can be programmed to target any RNA or DNA, and it is used for a long time for gene editing. To date, the CRISPR system was used exclusively in-vitro with individual cells, cell colonies and embryos. To be used in patients CRISPR system must be delivered into every cell of a patient. Direct injection of the CRISPR system into the blood system results in the fast and complete destruction of its components without cellular uptake.

PO-Laboratories developed carefully nanoengineered vehicles for the CRISPR-Cas system, which allows the use of this fantastic system in multicellular organisms such as humans and animals. This opens a new era of therapy by targeting the genome of any pathogen, and in fact, it is the first reliable antiviral therapy. We call this platform CRisper Intracellular Delivery System – CRIDS.
Programmable drug -COVID-19
Programmable Drug:

A drug that is programmable against a particular virus or bacteria - this sounds quite fantastic. However, in everyday language of geneticists "programmable" is quite common expression. Genome of any organism is the program by itself, so scientists who edit the genome really do the programming of a new sequences to modify the organism, or to cure genetic disease. There are different software developed to search and compare genetic sequences, to match sequences in the genome to particular proteins and so on. This makes computers and software essential for genome research. The same technique is applicable to the CRIDS drugs, because crRNA must be programmed to target a particular genome. This makes CRIDS a "Programmable" drug.

How to program CRIDS  drug:

  • Find or sequence the genome of a virus.
  • In this genome choose a unique sequence for this particular virus to target.
  • Create the complimentary sequence to the target.
  • Complete it with the base crRNA sequence.
  • Order or synthesize the programmed crRNA.
  • Encapsulate into CRIDS, test and use.

DNA -COVID-19 mutation
How about SARS-CoV-2 mutations?

It is true, the virus mutates fast. There are over 30 strains of it to May 2020. This poses a big problem for vaccine creation, because mutations mostly result in modifications in envelope protein. This requires immune system to have antibodies targeted to proteins of all SARS-CoV-2 strains, which is difficult or impossible. A secondary wave of SARS-CoV-2 pandemic is also possible just because of that.
Besides, mutations do not occur in vital regions of the virus genome, most likely because such mutations result in a strain not able to reproduce itself. Those regions in the viral genome make excellent targeting points for CRIDS therapeutic formulation.
In addition, with the same injection a patient may receive CRIDS formulation targeted to numerous points in the genome of the same virus which makes any mutations insignificant to the successful therapy.

CRIDS
Therapy

The developed by PO-Laboratories CRIDS antiviral system is not a substitute for vaccination of the population.
However, this is the first direct antiviral therapeutics, and during a pandemic, when a vaccine is not available yet, patients in a serious condition should be treated with CRIDS system, this will limit or eliminate patients’ complications and deaths.
In some cases people from a higher risk groups, as medical personal, may be treated with CRIDS antiviral system as a prevention measure.
We developed CRIDS antiviral system as an intravenous injectable formulation, however there are other possible forms of administration.

CRIDS2 nanoparticle
CRIDS Technology

PO-Laboratories developed a theory and then a highly successful technology of the drug delivery vehicle.
The CRIDS nanotechnology involves the synthesis of a “giant” macromolecular complex that includes a payload, resulting in nanoparticle formation. The payload is Cas - crRNA complex, its components or any other drug. The payload zipped in between the two polymer chains and located in the center of the nanoparticle. As a result, the payload is completely immobilized and isolated from external attacks by RNAses and ferments in the blood system.
CRIDS particles have very efficient cellular uptake with an adjustable rate. Several independent organizations and university researchers confirmed effective delivery into cells and through brain-blood barrier our intravenous (IV) nanoformulations, prepared by PO-Laboratories [2, 3]
The technology is described in all details and with numerous examples in our patent application “ANTI-COVID-19 THERAPEUTIC NANOFORMULATION AND MANUFACTURING TECHNOLOGY” No 3078021 [4].


CRIDS2 nanoparticles
CRIDS Advantages

  • CRIDS is the complete therapeutic treatment for COVID-19 patients as a formulation with intravenous or other administration;
  • Selectively destroys any vital point in SARS-CoV-2 (COVID-19) genome;
  • CRIDS targets the whole coronavirus family of viruses by use of crRNAs complementary to the conserved sequences of the family;
  • Targets multiple vital points in a viral genome;
  • Insensitive to virus mutations;
  • Highly selective and universal antiviral and antibacterial mechanism;
  • CRIDS opens a new era in the treatment of cancer and genetic diseases.
  • The CRIDS pharmaceutical formulation can be created as soon as sequence of a new virus is obtained, making urgent response possible;
  • No toxic chemicals nor heavy metals involved in CRIDS; all components are natural “green” ingredients – RNAs, DNAs, ferments and polysaccharides;
  • CRIDS system is fully metabolizable by cells, resulting in sugars, nucleotides and amino acids, the essential biomolecules of every organism;
  • The CRIDS system can be used to deliver other drugs into cells.

The Breadth of our Patent

The patent is entitled “Anti-Covid-19 Therapeutic Nanoformulation and Manufacturing Technology”.
Despite such a title, the patent covers a field which is far beyond the COVID-19 subject.
The claims are organized around the technology and include the use of any CRISPR system targeted to any pathogen genome, as well as the use of it for cancer and gene therapy in humans and animals.
In addition, we claim exclusive rights for the use of the technology with any payload, including any drugs, X-ray contrast agents, plasmids and other actives not only for therapy but also for gene editing, biotechnology, diagnostics, R&D and other uses.

The Business Niche of CRIDS

  • It is very difficult to overestimate the sales volume that could be generated from this invention.
  • We opened a new era of genome-targeted therapy. CRIDS could be used instead of “toxic” antibiotics to combat bacterial infections.
  • CRIDS could be used to combat cancer. CRIDS could be used to treat hereditary diseases.
  • However, the most important, CRIDS is the first reliable antiviral therapy in human history. The possible impact on human society could be similar to the discovery of penicillin by A. Fleming.
  • The CRIDS drug platform can be quickly programmed against a new virus that will appear sooner or later. Virus mutations present a major challenge for vaccine development, but not for CRIDS therapy.
  • Everyone on this planet is already in need of CRIDS products. The market is ready for sales, but it is empty. This provides a unique business opportunity for investors at very low risk.

Ant-COVID-19 therapeutic solution
References

  1. Yoshizumi Ishino, Mart Krupovic, Patrick Forterre Journal of Bacteriology Mar 2018, 200 (7) e00580-17; DOI: 10.1128/JB.00580-17;

  2. P. Duarte-Guterman, S.E. Lieblich, W. Qiu, J. Splinter, K. Go, L. Casanueva-Reimon, L. Galea, “Oxytocin has sex-specific effects on social behaviour and hypothalamic oxytocin immunoreactive cells but not hippocampal neurogenesis in adult Rats”, Hormones and Behavior 122 (2020) 104734;

  3. https://static1.squarespace.com/static/55bbf3f3e4b08b3622073685/t/58b8a14ce3df285075d187ff/1488494934288/170301-H2BB-Lived+it-the+Ovensa+Story.pdf , page 12;

  4. “ANTI-COVID-19 THERAPEUTIC NANOFORMULATION AND MANUFACTURING TECHNOLOGY” Patent application CA No 3078021, 04-19-2020.

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