Nanoformulated ART and CRISPR Eradication Strategy

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Solution Overview

Problem

Current treatments for HIV infection, particularly in eradicating the virus from viral reservoirs, are inadequate as they fail to achieve long-term undetectable viremia without antiretroviral therapy, necessitating a more effective therapeutic approach.

Innovation Solution

A combination therapy involving long-acting slow effective release antiretroviral therapy (LASER ART) and gene editing using CRISPR-Cas systems, specifically targeting HIV genomes in infected subjects to eradicate the virus by administering nanoformulated antiretroviral agents and CRISPR-Cas9/gRNA complexes to excise viral DNA sequences.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current antiretroviral therapy is used, then viral replication is suppressed during treatment, but the virus persists in viral reservoirs and rebounds after treatment cessation

Engineering Contradiction:

Improveviral suppression reliabilityVSAvoidduration of viral eradication

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent employs LASER ART to pre-treat and suppress viral replication in reservoirs before administering gene editing agents. This preliminary suppression reduces the viral burden and creates a more favorable environment for subsequent CRISPR-Cas9-mediated eradication, addressing the limitation of current therapy that fails to eliminate reservoirs

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses nanoformulated antiretroviral agents as intermediaries to deliver both suppressive therapy and gene editing components to viral reservoirs. These nanoformulations serve as a bridge between conventional ART and experimental eradication therapies, enabling controlled release and enhanced tissue penetration to reach latent reservoirs

Inventive Principle:

Principle #24Intermediary (Mediator)

2Duration of action of moving object

If long-acting slow effective release antiretroviral therapy is administered, then drug exposure in viral reservoirs is enhanced, but drug delivery to latent reservoirs remains challenging

Engineering Contradiction:

Improveduration of drug actionVSAvoiddrug delivery ease

Core Design Contradiction:

Duration of action of moving objectVSEase of operation

Solution Approach 1:

The patent modifies the pharmacokinetic parameters of antiretroviral drugs through myristoylation and nanoformulation, transforming short-acting drugs into long-acting formulations. This changes the release profile from rapid clearance to slow sustained release, maintaining therapeutic concentrations in reservoirs over extended periods while improving delivery through enhanced tissue penetration

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs composite nanoformulations that combine antiretroviral drugs with lipid-based carriers and targeting moieties. These composite structures enable both long-acting sustained release and improved delivery to latent reservoirs by combining the advantages of different material systems - the drug provides antiviral activity while the nano carrier provides extended circulation and enhanced tissue penetration

Inventive Principle:

Principle #40Composite materials

3Manufacturing precision

If gene editing agents are administered alone, then viral DNA can be targeted, but insufficient viral suppression occurs during the editing process

Engineering Contradiction:

Improveviral DNA excision precisionVSAvoidviral suppression reliability

Core Design Contradiction:

Manufacturing precisionVSReliability

Solution Approach 1:

The patent merges conventional antiretroviral suppression therapy with gene editing into a unified combination regimen. The ART component continuously suppresses viral replication while CRISPR-Cas9 targets and excises integrated proviral DNA. This merging of mechanisms addresses both active replication and latent reservoirs simultaneously, providing both immediate suppression and durable eradication

Inventive Principle:

Principle #5Merging (Combining)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach demonstrates the potential for complete eradication of HIV from infected subjects, as evidenced by undetectable viral loads and absence of viral rebound, with improved pharmacokinetic profiles and targeted reservoir targeting, indicating a significant advancement in HIV treatment.

Implementation Method 1

gene editing using CRISPR-Cas systems, specifically targeting HIV genomes in infected subjects to eradicate the virus by administering nanoformulated antiretroviral agents and CRISPR-Cas9/gRNA complexes to excise viral DNA sequences

Methodology Applied

Scientific EffectCRISPR-Cas9 gene editing:

Implementation Method 2

long-acting slow effective release antiretroviral therapy (called LASER ART)

Methodology Applied

Scientific EffectLong-acting slow effective release (LASER):

Data Source

PatentUS20200140865A1An HIV-1 eradication strategy employing nanoformulated Anti-retroviral drugs and gene editing agents

Publication Date: 2020.05.07 BOARD OF RGT UNIV OF NEBRASKA

AI summary

Methods of eliminating a retrovirus from a subject utilize nanoformulated anti-retroviral compounds and gene editing agents. Compositions comprise at least one anti-retroviral compounds, at least one gene-editing agent, or combinations thereof.