AAV-Free 시스템, LNP에 의한 유전자 편집, 바이러스 유사 입자 및 체내 직접 유전자 프로그래밍 - 기술, 파이프라인 및 시장 전망(2025-2045년)

Executive Summary / Description

In-vivo gene therapy is entering a second revolution:

moving beyond AAV to programmable, redosable, tissue-precise, immune-silent platforms capable of editing, replacing, or modulating genes directly inside the body.

Core innovation shift:

Fixed payload -> programmable genomic software delivered in vivo.

Critical drivers:

• Improved gene editors (base, prime, epigenome writers)
• LNP and exosome-mimetic delivery breakthroughs
• Safe systemic delivery replacing viral permanence
• Off-the-shelf, titratable dosing
• Multi-organ genome access (CNS, muscle, liver, immune system)

Primary therapeutic goals

• Treat rare & monogenic diseases
• Reverse common diseases at genotype-level (cardiometabolic, liver, neuro)
• Enable in-body cell therapy (CAR-T in vivo)
• Engineer precision organ regeneration

Global Market Forecast

• 2024: ~$10-12B
• 2030: $55-75B
• 2040: >$150B
• 2045: $300B+

Technology Understanding

Key Delivery Modalities: Category with Mechanism and Examples

• LNPs : Lipid carriers (RNA, DNA, protein) : Moderna, Beam, Intellia, Pfizer
• Polymer nanoparticles : Biodegradable gene carriers : Verve, Scribe partnerships
• Virus-like particles (VLPs) : Delivery without viral genome : VLP Therapeutics, Prime VLP systems
• Engineered exosomes : Bio-stealth delivery : Evox, Codiak IP heritage
• Hybrid systems : LNP + peptides + targeting ligands : Precision Biosciences, Sana
• Bacteriophage-derived vectors : Next-gen viral shuttles : Select pioneers + academia

Editing & Modulation Payloads

• CRISPR/Cas variants (Cas9, Cas12, CasX)
• Base editors
• Prime editors
• Epigenetic editors (CRISPRoff, dCas9-KRAB, gene silencing)
• RNA editors (ADAR systems)
• CRISPR-transposase insertion systems
• Oligonucleotide gene modulation (siRNA, ASO, saRNA)

Engineering Constraints & Innovations

• Tissue targeting ligands
• Immune stealth lipid libraries
• Machine-learning lipid screening
• Transient editor exposure windows (safety)
• Self-disappearing editors
• Single-infusion circuit-reactivation systems

Applications Spectrum

• Rare genetic diseases : Hemophilia, DMD, metabolic disorders
• Common diseases : Cardiometabolic gene edits (PCSK9, ANGPTL3)
• Oncology : In-vivo CAR-T, immune rewiring
• CNS : Huntington's, ALS, Alzheimer's risk genes
• Hematology : In-body reprogramming vs ex-vivo editing
• Regenerative Medicine : Fibrosis reversal, hepatocyte regeneration
• Aging & Longevity : Klotho, telomerase, mitochondrial biogenesis

Table of Content

1. Introduction

• 1.1 Evolution from AAV to programmable systems
• 1.2 Technology adoption curve
• 1.3 Clinical acceleration signals

2. Biology & Mechanistic Basis

• 2.1 Cell entry and endosomal escape
• 2.2 Transient vs permanent editing models
• 2.3 Off-target & genomic stability controls
• 2.4 Immune tolerance & AAV resistance bypass

3. Delivery Technologies

• 3.1 Lipid nanoparticle engineering
• 3.2 Polymer nanocarriers
• 3.3 Engineered exosomal systems
• 3.4 VLP-based cargo delivery
• 3.5 Hybrid synthetic-biologic systems
• 3.6 Non-viral CNS penetration maps

4. Gene Editing Toolkit

• 4.1 CRISPR classes & next-gen editors
• 4.2 Base & prime editing clinical horizon
• 4.3 Epigenome rewiring in vivo
• 4.4 Self-limiting gene circuits
• 4.5 Large-gene delivery breakthroughs

5. Clinical Landscape

• 5.1 Late-stage assets
• 5.2 Mid-stage programs
• 5.3 Early pipeline & academic pathways
• 5.4 Safety profiles emerging
• 5.5 Target tissue landscape

6. Market Analysis

• 6.1 TAM by modality and indication cluster
• 6.2 Pricing & reimbursement evolution

7. Competitive Landscape

• 7.1 Technology archetypes
• 7.2 Partnering & licensing matrix
• 7.3 M&A potential

8. Forecast & Scenarios

• 8.1 Base case
• 8.2 Accelerated adoption
• 8.3 Supply-chain constrained scenario

9. Future Outlook

• 9.1 In-vivo -> in-silico dosing optimization
• 9.2 Organ regeneration via gene rewiring
• 9.3 Gene therapy + AI health twin integration

10. Appendix