Leaders in Pharmaceutical Business Intelligence (LPBI) Group

Correspondence on Leadership in Genomics and other Gene Curations: Dr. Williams with Dr. Lev-Ari

Authors: Stephen J Williams, PhD and Aviva Lev-Ari, PhD, RN

RE:

• Leadership in Genomics: VarElect – Variants in Disease and UCSC Genome Technology Center

Reporter: Aviva Lev-Ari, PhD, RN

• Innovative Genomics Initiative (IGI)  2016 CRISPR WORKSHOP: PRACTICAL ASPECTS OF PRECISION BIOLOGY, UC, Berkeley, July 11-15, 2016

Reporter: Aviva Lev-Ari, PhD, RN

• CRISPR – genecards.org, UCSC, NM/OK, Caribou BioSciences

Author: Aviva Lev-Ari, PhD, RN

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From: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Date: Thursday, February 18, 2016 at 12:39 AM

To: “Dr. Katie Katie Siafaca” <info@newmedinc.com>

Subject: Re: In light of — >>>>>> Leadership in Genomics: VarElect ­ Variants in Disease and UCSC Genome Technology Center | Leaders in Pharmaceutical Business Intelligence

Leadership in Genomics: VarElect ­ Variants in Disease and UCSC Genome Technology Center

http://pharmaceuticalintelligence.com/2016/02/17/leadership-in-genomics-varelect-variants-in-disease-and-ucsc-genome-technology-center/

• There are important resources in the link above. 
• Gene therapy is the new trend.
• In Immune-Oncology – T Cell Reseptor Like (TCRL) is the new trend. 
• 5th generation is CAR-T

No one said it is not huge task. A very small piece is needed – which one ???

@@@

From: “Dr. Katie Katie Siafaca” <info@newmedinc.com>

Reply-To: “Dr. Katie Katie Siafaca” <info@newmedinc.com>

Date: Wednesday, February 17, 2016 at 11:11 PM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: re: In light of — >>>>>> Leadership in Genomics: VarElect ­ Variants in Disease and UCSC Genome Technology Center | Leaders in Pharmaceutical Business Intelligence

Hi Aviva,

I am not sure what is being proposed here.  In the cancer area, there are at least 1,200 genes implicated somehow in this disease and new ones are reported every day.  This is a colossal task!

Katie

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From: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Date: Wednesday, February 17, 2016 at 10:34 PM

To: “Stephen Williams, PhD” <sjwilliamspa@comcast.net>

Cc: “Dr. Larry Bernstein” <larry.bernstein@gmail.com>, Gerard Loiseau <gerard.loiseau@bluewin.ch>, “Dr. Katie Katie Siafaca” <info@newmedinc.com>

Subject: In light of — >>>>>> Leadership in Genomics: VarElect ­ Variants in Disease and UCSC Genome Technology Center | Leaders in Pharmaceutical Business Intelligence

Dear Dr. Williams,

HERE I am thinking LOUD

Is it possible to go to the dashboard, all posts and click on your Name, you will get the Universe of ~200 articles that you published.

HOW one could search or one needs to visually glance at the title of each — so as to pull a subset of posts that are dedicated to a GENE.

Create an Excel File, place each gene inside and go to Weizmann Institute’s genecards.org and pullout from them respective data on that gene

By so doing we will have LPBI’s Gene Inventory which we could reference in the Drug Discovery process, we do more and more, as we are aggregating all Biologics under the Joint Venture with SBH Sciences, Inc.

In light of :

Leadership in Genomics: VarElect ­ Variants in Disease and UCSC Genome Technology Center

http://pharmaceuticalintelligence.com/2016/02/17/leadership-in-genomics-varelect-variants-in-disease-and-ucsc-genome-technology-center/

My Questions are:

1. HOW could we take this “to be create Excel File” to be published a PAGE, Password Protected as your Curation, it needs to have a Parent or a Hierarchy of Nesting in the Website architecture

And subject that to your our search into New Medicine, Inc. NM/OK DB for data complementarity compilation?

2. What Foundation Medicine, Now Roche, does have vs. Weizmann Institute’s genecards.org

 http://www.genecards.org/

I read and I visited genecards.org

Most interesting is

http://www.genecards.org/cgi-bin/carddisp.pl?gene=ALB#drugs_compounds

3. Will Weizmann Institute’s genecards.org be interested in New Medicine, Inc., NM/OK DB?

4. I have explored with Foundation Medicine, Now Roche regarding New Medicine, Inc., NM/OK DB and their reply was that they focus ONLY on Genomics data in Cancer, thus,, no interest in New Medicine, Inc. NM/OK DB, there

5. What is in Weizmann Institute’s genecards.org that is NOT in UC Santa Cruz DBs ?

http://pharmaceuticalintelligence.com/2016/02/17/leadership-in-genomics-varelect-variants-in-disease-and-ucsc-genome-technology-center/

6. If you would take EACH ENTRY in this “to be create Excel File” and supplement it with

6.1 Weizmann Institute’s genecards.org

6.2 UC Santa Cruz Dbs

6.3 New Medicine, Inc., NM/OK DB – given this is a GENE in the cancer implication

6.4 A RECORD of the outputs from 6.1, 6.2, 6.3

7. THEN we could target 6.4 for CRISPR and go to 

http://rna.berkeley.edu/crispr.html

http://rna.berkeley.edu/contact.html

DNA interrogation by the CRISPR RNA-guided endonuclease Cas9

• Samuel H. Sternberg, Sy Redding, Martin Jinek, Eric C. Greene & Jennifer A. Doudna Nature 507, 62–67 (06 March 2014) doi:10.1038/nature13011

http://www.nature.com/nature/journal/v507/n7490/full/nature13011.html

and

http://rna.berkeley.edu/translation.html

http://alumni.berkeley.edu/california-magazine/winter-2014-gender-assumptions/cracking-code-jennifer-doudna-and-her-amazing

8. Doudna started her professorship at Yale University in 1994. While the group was able to grow high-quality crystals, they struggled with thephase problem due to unspecific binding of the metal ions. One of her early graduate students and later her husband, Jamie Cate decided to soak the crystals in osmium hexamine to imitate magnesium. Using this strategy, they were able to solve the structure, the second solved folded RNA structure since tRNA.^[9][10] The magnesium ions would cluster at the center of the ribozyme and would serve as a core for RNA folding similar to that of a hydrophobic core of a protein.^[5]

9. In 2015, Doudna gave a TED Talk about the bioethics of using CRISPR. ^[13]

“Jennifer Doudna TED Talk”.

Lastly,

10. Caribou BioSciences

http://cariboubio.com/application-areas/therapeutics

Precision medicines have the ability to transform healthcare and treat a myriad of unmet medical needs. The Caribou technology platform has the ability to generate transformative medicines in multiple different market segments.

Our current therapeutic areas of exploration include anti-microbials, animal health, and therapeutic bioproduction.

Human therapeutics

In 2014, Caribou co-founded Intellia Therapeutics to develop curative medicines utilizing the Caribou CRISPR-Cas9 platform. Rachel Haurwitz, President and Chief Executive Officer of Caribou, is a member of Intellia’s Board of Directors.

Intellia is developing human gene and cell therapies for both ex vivo and in vivo applications using CRISPR-Cas9 gene editing technology. Near-term ex vivo applications include the treatment of blood disorders and cancer. In January 2015, Intellia announced a five-year research and development collaboration with Novartis to accelerate the ex vivo development of new CRISPR-Cas9-based therapies using chimeric antigen receptor T cells (CARTs) and hematopoetic stem cells (HSCs).

Any thoughts for me?

Aviva Lev-Ari, PhD, RN

@@@

From: “Stephen Williams, PhD” <sjwilliamspa@comcast.net>

Date: Wednesday, February 17, 2016 at 6:42 PM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: Re: Leadership in Genomics: VarElect ­ Variants in Disease and UCSC Genome Technology Center | Leaders in Pharmaceutical Business Intelligence

Every post I do that contains a gene in the post is curated with a link to genecards database so later it not only can be searched but is an integrated knowledge-analysis base integrated with a knowledge and fully integrated Omics database as gene cards . org also contains protein, structure and functional databases. 

This is where I always felt the power of LPBI was in the genomic space, integration of a deep analysis curated database 

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From: AvivaLev-Ari@alum.berkeley.edu

To: mfeldman@stanford.edu

Cc: sjwilliamspa@comcast.net

Sent: 2016-02-17 18:01:03 GMT

Subject: Leadership in Genomics: VarElect ­ Variants in Disease and UCSC Genome Technology Center | Leaders in Pharmaceutical Business Intelligence

Which of them did you use already?

http://pharmaceuticalintelligence.com/2016/02/17/leadership-in-genomics-varelect-variants-in-disease-and-ucsc-genome-technology-center/

Aviva Lev-Ari, PhD, RN

@@@

From: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Date: Wednesday, February 17, 2016 at 5:59 PM

To: “Stephen Williams, PhD” <sjwilliamspa@comcast.net>

Cc: “Dr. Katie Katie Siafaca” <info@newmedinc.com>

Subject: Fwd: Leadership in Genomics: VarElect – Variants in Disease and UCSC Genome Technology Center | Leaders in Pharmaceutical Business Intelligence

We will use these two platforms

http://pharmaceuticalintelligence.com/2016/02/17/leadership-in-genomics-varelect-variants-in-disease-and-ucsc-genome-technology-center/

Aviva Lev-Ari, PhD, RN

@@@

From: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Date: Wednesday, February 17, 2016 at 3:42 PM

To: “Stephen Williams, PhD” <sjwilliamspa@comcast.net>

Subject: Re: The Science Coming in 2016 – OpenMind

I read and I visited gene cards.org

Most interesting is

http://www.genecards.org/cgi-bin/carddisp.pl?gene=ALB#drugs_compounds

Aviva Lev-Ari, PhD, RN

@@@

From: “Stephen Williams, PhD” <sjwilliamspa@comcast.net>

Date: Wednesday, February 17, 2016 at 1:46 PM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: Re: The Science Coming in 2016 – OpenMind

I want you to go to http://www.genecards.org/ then pick a gene and scroll down.  You will see a database there for CRISPR products available from different distributors including Qiagen, Promega, Fisher Scientific, Santa Cruz as well as others.  This seems to be already underway.  It is possible to copy what these companies are already doing but I don’t see the business advantage in that.  Please remember that 3D printing involves layering a of first and second dimension to a third dimension product.  So for instance the cell would be the “first dimension” even though it is three dimensional but the effect of layering MULTIPLE layers of cells is what gives their 3D effect.  The biomaterial you put in each tube is, in essence, your first dimension you are going to layer into a multilayered “3D” structure.

DNA can be made by synthesizers, there is no need to bioprint it, especially short fragments and in fact you wouldn’t.  They can handle even longer material.  Possibly if you want to replace a whole nucleosome but the chemistry is not there.  That is fine working with Jennifer Duodna making a library of small guide RNA’s to be used in CRISPR however it seems to be in process as I said before.  This would need to be done with her system and optimized for her system. You would also need a huge operation to do validation as well.  In addition the number of mutations, SNPs, variants are extremely large and many are not disease specific.

Again each would have to be validated.  In addition, unless you are doing embryo manipulation, you will need to partner with a company that has a good gene delivery system.  This will cost $, probably around 500 million. 

@@@

From: “Aviva Lev-Ari” <avivalev-ari@alum.berkeley.edu>

To: sjwilliamspa@comcast.net

Cc: “Gerard Loiseau” <gerard.loiseau@bluewin.ch>, “Dr. Larry Bernstein” <larry.bernstein@gmail.com>

Sent: Tuesday, February 16, 2016 4:48:54 AM

Subject: The Science Coming in 2016 – OpenMind

This gene fragment in red color — I am suggesting to build with 3D BioPrinting,

at the Oligonucleotide level.

Create a library of fragments for the most common mismatch in transcriptions, as well as on demand for rare deletions.

Per University of California, Santa Cruz, Database of Variations, prepare an INVENTORY of GENE REPAIR PARTS, manage the inventory by Analytics, where each part was implanted and monthly interval monitoring of segment incorporation and new function of protein folding achieved.

Trace the genetic therapy achieved by Gene editing.

Any comments??

https://www.bbvaopenmind.com/en/the-science-coming-in-2016/?utm_source=facebook&utm_medium=techreview&utm_campaign=MITcompany&utm_content=Science2016