Brain-Tools

James Summerton, Ph.D. (Biochemistry)

James Summerton

After high school in Collbran, Colorado (Don Moss and I were classmates in that high school), I received a BS in chemistry at Northern Arizona University, and then went to medical school at the University of Colorado School of Medicine in Denver.  But since my interest lay in doing medical research at the molecular level, I soon realized that training for an MD was not the optimal way to go and so I switched to a Ph.D. program in biochemistry at the University of Arizona School of Medicine.

In 1969, while still a graduate student, I came up with the idea that any virus might be safely treated by selectively blocking a key genetic sequence specific to that virus.  In 1973 I received a Ph.D. in biochemistry, and in 1974 I began an NIH postdoctoral fellowship at Berkeley, where I began developing my first gene-blocking agents.  In 1976 I continued toward that same goal as a research associate in Denver, where I met and soon married Patricia Rusnak (Pat).  In 1978  I was offered a research faculty position in the Biochemistry-Biophysics Department at Oregon State Univ. in Corvallis, Oregon, so Pat and I moved to Corvallis where I continued my quest to develop gene-blocking agents for modulating the activity of selected genes.

In 1980 I left Oregon State Univ. to found ANTIVIRALS, Inc. (AVI) in my basement.  AVI was the pioneer company focused on developing agents for specifically modulating the activity of selected genes.  During this period Pat took up computer programming and accounting in order to support our family (by then with three kids) while I took care of the kids and worked to launch my new company and carry out work on a new second-generation gene-modulating technology.  On 1 January 1985 I devised a very novel third-generation structural type with much improved properties.  By the late-1980s I and my co-workers at ANTIVIRALS, Inc. completed development of those advanced third-generation agents, which constitute radically redesigned genetic material suitable for specifically blocking any selected gene transcript in biological systems.  By the mid-1990s these gene-modulating agents, called “Morpholino antisense oligos”,  http://en.wikipedia.org/wiki/Morpholino, were developed and refined to the point that they could reliably serve as broadly applicable tools for genetic research.

In 1996, preparatory to our initial public stock offering (IPO), the Board of Directors of  ANTIVIRALS Inc. (AVI) decided it was time to focus on selected therapeutic applications of these Morpholino oligos  – but I contended that specific therapeutic applications were premature because nearly all of the available experimental evidence indicated that no antisense oligo type, including our Morpholinos, could yet be reliably delivered into the proper subcellular compartments within cells in living animals.

In 1997, after AVI went public (later changed to AVI BioPharma, AVII on the NASDAQ stock exchange, and recently changed to Sarepta Therapeutics), I departed  AVI  to launch a spinoff company, GENE TOOLS, LLC, where our focus was on:

  1. producing custom Morpholino antisense oligos for research applications; and,
  2. improving delivery of Morpholinos into cells in culture and achieving delivery in animals, including humans.

GENE TOOLS, LLC (www.gene-tools.com) is the sole company that produces custom Morpholino antisense molecules for use as research reagents.  Each week  we design, produce, and ship to customers worldwide about 200 to 300 different custom-sequence Morpholinos, each targeted against a different genetic sequence.  These Morpholinos constitute the most specific, effective, and stable of all gene modulating agents.  In the past decade these Morpholinos have revolutionized the field of developmental biology, and there are now over 5,000 published papers where these Morpholinos were used as key research tools, see:
www.gene-tools.com/Publications/

Since 1998 we have developed 5 cell delivery systems, each better than the last, and in 2008 we finally completed development of and launched Vivo-Morpholinos (designed by Dr. Yongfu Li of GENE TOOLS) which contain a special end structure that delivers Morpholinos into cells in animals.  While these Vivo-Morpholinos are adequate for research use in small animals,  regrettably these Vivo-Morpholinos are not as safe or efficient as needed for broad therapeutic applications in humans, nor are they effective for delivery across the blood/brain barrier.

However, I hope to soon remedy these delivery limitations by virtue of an entirely new multi-component receptor-mediated transporter system which I have been working on for several years.  This new delivery system is explicitly designed to transcytose across the blood/brain barrier.  If and when this new delivery system achieves its goals (hopefully in 2013 or 2014), I believe this will quickly enable development of safe and effective antisense treatments for most viral diseases, for multiple genetic diseases (such as muscular dystrophy, progeria, and others), and it should also afford safe and effective custom treatments for a host of other currently intractable diseases that plague humanity (such as autoimmune diseases).

Alzheimer’s application

Recently published research by Dr. George Bloom and co-workers at the Univ. of Virginia indicates that the progressive destruction of brain cells which occurs in the brains of Alzheimer’s patients requires both beta-amyloid present outside the brain cells and the presence of Tau protein within those brain cells (see: Nature 485 651 (2012); and google the phrase:  “amyloid is the trigger and tau is the bullet”).  Stated differently, if Tau protein is not present within the brain cells then the beta-amyloid outside the brain cells apparently does no harm. Further, it is known that after embryogenesis apparently the Tau protein is no longer required for normal brain function.

Therefore, there is good reason to expect that one of
GENE TOOLS’ Morpholino oligos, targeted against the mRNA coding for Tau protein and having attached transporter elements effective to deliver across the blood/brain barrier, may effectively halt the progressive destruction of brain cells in Alzheimer’s patients.  When combined with MSF for reviving memory in damaged brains, this combination of a Morpholino to delete Tau and MSF to revive memory may convert Alzheimer’s from a certain death sentence to a treatable chronic disease wherein the patient is capable of normal or near normal function for decades to come.