Safe delivery of crispr and other gene therapies to large fractions of somatic cells in humans and animals

Inactive Publication Date: 2020-10-15
HANLEY BRIAN P
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0067]The invention has application to two important areas of clinical therapeutics, CRISPR gene therapy and general gene therapy. Both areas are of high importance to society and improvements in this area can provide significant benefit. Therefore, the foregoing is considered as illustrative only of the principles of the invention. Further, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired to limit the invention to the exact disclosure shown and described, and accordingly, all suitable modifications and equivalents may be resorted to, falling within the scope of the invention.
[0068]Part 1 of this specification addresses a major problem in gene therapy delivery, which is that if one attempts to deliver the required dose of a gene therapy for conditions, such as muscular dystrophy that require

Problems solved by technology

This can also duplicate multi-organ failure which is often triggered by DAMP overstimulation.
It is noted that a potentially dangerous off target event does not equal cancer.
There are two problems that obstruct the development of gene therapy in general and ‘Clustered Regularly Interspaced Short Palindromic Repeats’ (CRISPR) gene therapy in particular.
These problems are: delivery of DNA or RNA to sufficient cells in a human body; and overlong expression of CRISPR.
Unfortunately, very few people, including physicians and scientists who work with microbial methods for treatment of cancer, are aware of the uniqueness of human immunology relative to immune syst

Method used

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embodiment

DESCRIPTION OF EMBODIMENT

The Preferred Embodiment of Part 1

[0070]The preferred embodiment of Part 1 of the invention is a method comprising delivery of drugs to inhibit the immune system, the method comprising the steps.[0071]a. An inhibitor of NFκB.[0072]b. An inhibitor or IRF3, TLR3, TLR4, and TLR7 / 8. The SSRI, sertraline, is preferred due to lower toxicity. Other SSRI or SNRI drugs may also prove to work for this purpose.[0073]c. A TLR9 inhibitor if it is required.[0074]d. A TNFα inhibitor.[0075]e. An mTOR inhibitor.[0076]f. An NADV for delivery of nucleic acid into cells of a living animal.

The Preferred Embodiment of Part 2

[0077]The preferred embodiment of Part 2 of the invention is a structure comprising:[0078]a. An expression vector plasmid containing CpG-ODNs.[0079]b. An expression vector plasmid with a promoter dependent on a TetR system.[0080]c. An expression vector plasmid with a promoter, and multiple protein coding sequences with CHYSEL linkers between them.

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Abstract

A method for making it possible to deliver nucleic acid sequences to a large fraction of, or even 99.9% and more of the cells in a human body without near certainty of killing the recipient. It can be applied to safely deliver any gene therapy. This invention comprises a set of known compounds, many of them already approved, combined in novel ways to prevent immune system reaction to levels of delivery vehicle (capsid or synthetic carrier) introduced into the body that can be 5 or more orders of magnitude higher than has been demonstrated to cause human death. When used in concert with the disclosed CRISPR expression control method, this method can improve expression and allow better control over the gene therapy's target activity.

Description

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Claims

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Application Information

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Owner HANLEY BRIAN P
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